Niklas Klümper @niklas_kluemper Twitter profile

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Niklas Klümper

@niklas_kluemper

1 year

Happy to share our work: Membranous NECTIN-4 expression frequently decreases during metastatic spread of urothelial carcinoma and is associated with enfortumab vedotin resistance @CCR_AACR Follow our tweetorial about this clinically important data 1/12

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcin...

AbstractPurpose:. The antibody–drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients...

aacrjournals.org

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Niklas Klümper

@niklas_kluemper

6 months

HER2 heterogeneity is important for HER2-ADC response. ADC response depends on its target gene expression🎯 EV response depends on NECTIN4 (PMID: 36534531) but heterogeneous NECTIN4 in mUC has not yet been systematically investigated! @OncoAlert @urotoday

Targeting HER2 heterogeneity in breast and gastrointestinal cancers

About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of...

www.cell.com

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Niklas Klümper

@niklas_kluemper

1 year

We're grateful to @EUplatinum for featuring our insights on the power of integrating Nectin-4 PET/CT in guiding Nectin-4 targeting therapies like Enfortumab vedotin for patients with met UC. #PrecisionMedicine Follow our tweetorial 1/6

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Niklas Klümper

@niklas_kluemper

1 year

Happy to share our work: Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma @JAMAOnc . See our tweetorial and the terrific editorial by @ggebraelmd @GliceidaGalarza @neerajaiims @urotoday 1/7

JAMA Oncology

@JAMAOnc

1 year

Integrating on-treatment mGPS (CRP + albumin) for a more holistic and patient-centered therapy monitoring in addition to radiological staging may improve outcome prediction for patients with mRCC. @saal_jonas @niklas_kluemper @IEO_HolzelLab @UniklinikBonn

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Niklas Klümper

@niklas_kluemper

1 year

First-in-human study of NECTIN-4 PET/CT to non-invasively capture membranous NECTIN4 expression in met. urothelial carcinoma 🎯 Important data as we have previously shown a correlation of membranous NECTIN-4 with EV response (PMID: 36534531) @CCR_AACR .

First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced...

AbstractPurpose:. Nectin-4 is an emerging biomarker for cancer diagnosis and therapy. Recently, enfortumab vedotin (EV) was approved by the FDA as the first nectin-4 targeting antibody–drug conjugate...

aacrjournals.org

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Niklas Klümper

@niklas_kluemper

3 months

Transformative results of EV-302 nicely summarized in this @NEJM Quick Take video! But how to move forward for mUC now?🤔 Identifying biomarkers of resistance to EV+PEM is key to further improve outcomes for mUC 🔎 The most intuitive biomarker for predicting response/

NEJM

@NEJM

3 months

Among patients with advanced urothelial cancer, 5-year survival with first-line platinum-based chemotherapy is relatively low. Enfortumab vedotin plus pembrolizumab may improve outcomes. Research findings are summarized in a new Quick Take video.

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Niklas Klümper

@niklas_kluemper

6 months

Promising data for HER2 ADC DV for mUC: Again target gene expression correlates with ADC response: ORR 62.2% with HER2 IHC 2+/ FISH+ or IHC 3+ versus 39.6% for IHC 2+FISH-🎯Similar results for mUC in DESTINY-PanTumor02 for T-DXd! @OncoAlert @urotoday

Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor...

PURPOSE To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti–human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin...

ascopubs.org

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Niklas Klümper

@niklas_kluemper

8 months

Great paper by Bosi et al: Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response🎯Co-expression of various ADC targets (e.g. NECTIN4) again highlights potential for agnostic ADC therapy @OncoAlert @urotoday

Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response

Antibody-drug conjugates (ADCs) are a rapidly expanding class of compounds in oncology. Our goal was to assess the expression of ADC targets and potential downstream determining factors of activity...

www.ejcancer.com

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Niklas Klümper

@niklas_kluemper

1 year

More exciting data on the efficacy of ADC for active brain mets. There is also a case series demonstrating Enfortumab vedotin response in UC brain mets () by @tompowles1 & Team. We should start to design #ADC trials for this hard-to-treat population 🎯

First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients

Enfortumab vedotin (EV), an antibody–drug conjugate directed against Nectin-4, significantly prolonged survival compared to standard chemotherapy in patients with locally advanced or metastatic...

www.ncbi.nlm.nih.gov

Paolo Tarantino

@PTarantinoMD

1 year

Does T-DXd work in patients with active HER2+ BC brain metastases that have progressed on prior tucatinib? In this case series of 5 heavily pretreated patients, T-DXd had an intracranial response rate of 100%, including in tumors insensitive to tucatinib.

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Niklas Klümper

@niklas_kluemper

7 months

Thanks @ViktorGruenwald for highlighting our work on the value of NECTIN4 status to predict EV response at a stellar symposium with @PGrivasMDPhD @drenriquegrande @OncoBellmunt at @myESMO @OncoAlert @urotoday @CCR_AACR Predictive biomarkers are needed !

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcin...

AbstractPurpose:. The antibody–drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients...

aacrjournals.org

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Niklas Klümper

@niklas_kluemper

2 years

CRP flare 🔥! Longitudinal CRP kinetics predicts response to immunotherapy in NSCLC as early as 4 weeks after therapy start. Simple on-treatment biomarker to optimize monitoring. Chance for early therapy adjustments. Thanks to all collaborators! @docbald @IEO_HolzelLab @UniBonn

Journal for ImmunoTherapy of Cancer

@jitcancer

2 years

New #JITC short report: C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer @niklas_kluemper @Doc_Bald

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Niklas Klümper

@niklas_kluemper

1 year

Enfortumab vedotin has activity on brain metastases in UC! In line with observations from anti-Her2 ADC T-DXd in breast cancer with brain metastases (TUXEDO-1 trial). #ADC work against active CNS metastasis @ViktorGruenwald @Markuseckstein3 @tompowles1 .

First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients

Abstract: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, signif-icantly prolonged survival when compared with standard chemotherapy in patients with locally advanced...

www.preprints.org

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Niklas Klümper

@niklas_kluemper

6 months

Great to see EV+PEM being approved for 1L mUC based on EV-302 @tompowles1 !🎉To further improve outcomes precision medicine is needed. Great overview of future directions by @MattGalsky 🎯NECTIN4 again discussed to predict EV outcomes @OncoAlert @urotoday

Precision Medicine in Urothelial Carcinoma: Current Markers to Guide Treatment and Promising Future...

Current Treatment Options in Oncology - The treatment landscape for urothelial cancer has changed dramatically in the last 10 years, with the approval of several new treatments. At the same time,...

link.springer.com

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Niklas Klümper

@niklas_kluemper

3 months

Exciting study reveals correlation between Trop2 target expression and anti-Trop2 ADC SG response in TNBC! @JCO_ASCO @ASCOPost @PTarantinoMD Membranous target gene expression crucial for ADC efficacy! ➡️ well-established for Her2, Nectin4, and Folr1 ! We need to consider the

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Niklas Klümper

@niklas_kluemper

3 months

Great to see EV-302 data finally published @NEJM ! Big step for patients with metastatic UC with doubling in OS! ➡️Open questions are which patients in particular benefit from EV/P and which patients only achieve short-term response or have primary EV/P resistance? ➡️Prediction

NEJM

@NEJM

3 months

In a trial comparing enfortumab vedotin and a PD-1 inhibitor with chemotherapy in patients with untreated advanced or metastatic urothelial cancer, progression-free and overall survival nearly doubled with the experimental treatment. Full trial results:

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Niklas Klümper

@niklas_kluemper

2 years

Thrilled to share our work on the modified Glasgow prognostic score predicting prognosis in metastatic RCC (IMmotion151 trial) more accurately than the IMDC score! Published in @Annals_Oncology . Thanks to all collaborators! @IEO_HolzelLab @UniklinikBonn

In the phase III IMmotion151 trial of metastatic renal cell carcinoma the easy-to-implement...

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is relevant for the first-line treatment decision in patients with metastatic renal cell carcinoma (mRCC).1 The IMDC...

www.annalsofoncology.org

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Niklas Klümper

@niklas_kluemper

4 months

Activity of anti-Her2 ADC T-DXd for cerebral metastases is truly remarkable🧠📷 As these patients are often excluded from trials, it's crucial to conduct more ADC trials in this challenging population, e.g. like TUXEDO-1 @PTarantinoMD @ESMO_Open @oncoalert @urotoday @imedverse

ESMO Open

@ESMO_Open

4 months

In a meta-analysis of 10 studies by Michelin et al, published on @ESMO_Open , T-DXd was found associated with relevant intracranial activity among patients with breast cancer brain metastases (IC-ORR 61%, mPFS 15 months). Read the article here:

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Niklas Klümper

@niklas_kluemper

5 months

T-DXd with 56.3% ORR in HER2 IHC 3+ met. UC 🎯 Important validation that ADC efficacy depends on target gene expression. Same applies to other heterogeneously ADC targets like NECTIN4. Big step towards 1st tumor agnostic ADC approval @urotoday @Markuseckstein3 @ViktorGruenwald

Journal of Clinical Oncology

@JCO_ASCO

5 months

🌟🌟🌟 In DESTINY-PanTumor02, Trastuzumab deruxtecan showed durable responses across HER2-expressing solid tumors ➡️ #gyncsm #hpbcsm #blcsm @MDAndersonNews

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Niklas Klümper

@niklas_kluemper

1 year

Grateful for the incredible opportunity to participate in the #MCCR workshop by @EORTC , @AACR , and @myESMO . Huge thanks to the faculty and to the exceptional mentors of our group @NPortaStat , @giannatempopatr , and @Philippe_Bedard for their guidance and support! @achillebott91

EORTC

@EORTC

1 year

Class of 2023 #MCCRWorkshop . Thanks to the organising partners @EORTC - @myESMO - @AACR

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Niklas Klümper

@niklas_kluemper

1 year

Happy to share our Editorial @EUplatinum on the rational of pretreatment metastatic biopsy in met. UC ➡️Step towards precision oncology 🎯 Chance for improved ICB and EV response prediction @Markuseckstein3 @HolzelMichael @IEO_Bonn @UniBonn @UniklinikBonn

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Niklas Klümper

@niklas_kluemper

1 year

Another great example that for heterogeneously expressed targets like Her2 or Nectin4 (PMID: 36534531) the surface expression matters for ADC response - even across entities 🎯 Tumor agnostic therapy as a major step towards ADC precision oncology 💪🏼 @ViktorGruenwald @urotoday

Paolo Tarantino

@PTarantinoMD

1 year

#ASCO23 will take us to the agnostic ADC era. In the just released #HERALD phase 2 trial, 62 patients with 16 different advanced cancer types and detectable HER2 amp on ctDNA received T-DXd. ORR 56.6% DCR 90% Responses in 13 cancer types.

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Niklas Klümper

@niklas_kluemper

7 months

Great paper by @LDyrskjot ´s group @CCR_AACR ctDNA clearance following neoadjuvant chemo predicts excellent outcomes in MIBC. This results may pave the way for ctDNA-guided bladder preserving approaches. ctDNA comes closer to the clinic @OncoAlert @urotoday

Circulating Tumor DNA Analysis in Advanced Urothelial Carcinoma: Insights from Biological Analysis...

AbstractPurpose:. To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metasta...

aacrjournals.org

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Niklas Klümper

@niklas_kluemper

1 year

Happy to share our work: Early CRP kinetics predicts immunotherapy response in NSCLC in the phase III OAK trial @saal_jonas @JNCI_Now . Follow our tweetorial about this simple and easy-to-implement immunotherapy biomarker 1/7

Early C-reactive protein kinetics predicts immunotherapy response in non-small cell lung cancer in...

Abstract. Static biomarkers like programmed death-ligand 1 (PD-L1) are insufficient to accurately predict response to immune checkpoint inhibition. Therefo

academic.oup.com

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Niklas Klümper

@niklas_kluemper

7 months

In three Phase III trials (mUC: IMvigor211, mRCC: IMmotion151, NSCLC: OAK) immunotherapy prolonged OS when baseline serum albumin was >35g/L -> Prediction of less immune fitness via simple albumin measurement? @OncoAlert @ClinTransImmuno @Doc_Bald @IEO_Bonn

Clinical & Translational Immunology | ASI Journal | Wiley Online Library

We show in 3 different randomized trials, that serum albumin is a strong predictor of survival in patients with cancer treated with atezolizumab. The predictive value of serum albumin is independent...

onlinelibrary.wiley.com

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Niklas Klümper

@niklas_kluemper

3 months

Prediction of therapy response based on RECIST criteria only has limitations for the immunotherapy era! Longitudinal assessment of simple inflammatory 🔥blood biomarkers (CRP + albumin integrated into modified Glasgow Prognostic Score/ mGPS) provides complementary information

Niklas Klümper

@niklas_kluemper

1 year

Happy to share our work: Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma @JAMAOnc . See our tweetorial and the terrific editorial by @ggebraelmd @GliceidaGalarza @neerajaiims @urotoday 1/7

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Niklas Klümper

@niklas_kluemper

9 months

@sonpavde Great news! But how will EV compete with the other ADC (Trop2, Her2) and Erda. Predictive biomarkers urgently needed for mUC. We and others argue for incorporation of NECTIN-4 expression in future biomarker strategies @Dr_Aggen @CChuMD @DrRosenbergMSK

Scratching the Surface: NECTIN-4 as a Surrogate for Enfortumab Vedotin Resistance - PubMed

Clinical data with enfortumab vedotin (EV) suggest that most bladder cancers overexpress NECTIN-4. A recent article shows that NECTIN-4 membranous expression changes with progression to metastatic...

pubmed.ncbi.nlm.nih.gov

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Niklas Klümper

@niklas_kluemper

2 months

Happy to share or words of wisdom commentary @EUplatinum about ADC development for Penile squamous cell carcinoma (PSCC)! @JLinxweiler @Markuseckstein3 @Uroweb ➡️Targeting common antigens like TROP2 or NECTIN-4 is a promising avenue to develop tumor-agnostic ADC treatment in

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Niklas Klümper

@niklas_kluemper

2 years

C-reactive protein flare predicts response to immunotherapy in UC🔥Thus, early longitudinal CRP kinetics has predictive value across entities (also proven for RCC + NSCLC)! Thanks to all collaborators! @Markuseckstein3 @IEO_HolzelLab @IEO_Bonn @UniBonn

C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic...

Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especia...

www.ejcancer.com

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Niklas Klümper

@niklas_kluemper

9 months

Prognostication & monitoring are key to further develop therapies for mRCC! Excited to discuss our insights @EUplatinum on the role of IMDC and inflammatory biomarkers like mGPS (CRP + albumin) in current 1st line mRCC treatment @ViktorGruenwald @urotoday

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Niklas Klümper

@niklas_kluemper

2 months

Great news again! First agnostic ADC approval for anti HER2 #TDXd based on DESTINY-PanTumor02! @US_FDA Approval based on HER2-biomarker-selection, only HER2 IHC3+ solid tumors with no satisfactory alternative treatment options -> ADC targetability matters! Great news for

Paolo Tarantino

@PTarantinoMD

2 months

T-DXd is approved for the treatment of patients with ANY treatment-refractory HER2+ (IHC 3+) tumor, making of it the first agnostic ADC. Unlikely to be the last. Key priority: ensuring that HER2 testing is expanded across cancer types. Exciting times!

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Niklas Klümper

@niklas_kluemper

8 months

Great news for patients with met. UC! But do all patients benefit or what could be the role of predictive biomarkers for EV response like NECTIN4 status? @Markuseckstein3 @ViktorGruenwald @urotoday @OncoAlert @CCR_AACR

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcin...

AbstractPurpose:. The antibody–drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients...

aacrjournals.org

Tom Powles

@tompowles1

8 months

EV302- enfortumab vedotin and Pembrolizumab met its dual primary endpoints of OS and PFS with ‘clinically meaningful’ improvement versus chemotherapy in patients with previously untreated la/mUC.

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Niklas Klümper

@niklas_kluemper

4 months

It is remarkable how quickly nutrition influences the immune system! @NatureMedicine Diet - with its enormous influence on the gut microbiome - is also increasingly coming into the focus of cancer immunotherapy. More studies on dietary intervention needed! @ImmunoSens @OncoAlert

Ashish M. Kamat, MD, MBBS

@UroDocAsh

4 months

Divergent effect of diet on the immune system Ketogenic diet enriching for adaptive immune signatures (beneficial in cancer) Vegan diet -> for innate immune signatures @Nature

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Niklas Klümper

@niklas_kluemper

2 years

Early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimize therapy monitoring in patients with mRCC treated with immunotherapy. Thanks to the collaborators! @HolzelMichael @IEO_HolzelLab @Zeuschner_P @chariskalogirou

IEO_HölzelLab

@IEO_HolzelLab

2 years

CRP as biomarker to predict responses to immune checkpoint inhibitors in patients with metastatic renal cancer. Great potential for the clinic as simple and cost-effective. Congrats to @niklas_kluemper @UniklinikBonn and collaborators.

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Niklas Klümper

@niklas_kluemper

9 months

Exciting Update from EV301 trial! 🚀EV maintains survival benefit after ~2 years of follow-up. BUT: Who benefits most from EV?🎯 Our data suggest NECTIN4 as a promising predictive biomarker! @OncoAlert @urotoday @Markuseckstein3 @ViktorGruenwald #oncology

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcin...

AbstractPurpose:. The antibody–drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients...

aacrjournals.org

Guru P. Sonpavde, MD

@sonpavde

9 months

EV301 Phase III trial update (median follow-up ~2 years): Enfortumab vedotin (EV) maintained survival (HR 0.70, P = 0.00015), PFS (HR 0.63, P < 0.00001) and response rate (41.3% vs. 18.6%) benefit vs. chemotherapy in post-platinum and PD1/L1 inhibitors patients with metastatic

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Niklas Klümper

@niklas_kluemper

11 months

Thanks @urotoday for highlighting our work! Molecular urothelial subtypes remain stable during metastatic evolution. Potential implication for biomarker-stratified trial design in patients with met. UC 🎯 @AlexanderCoxMD @Markuseckstein3 @OncoAlert @UniklinikBonn @IEO_Bonn

UroToday.com

@urotoday

11 months

Molecular urothelial tumor cell subtypes remain stable during metastatic evolution. #BeyondTheAbstract Alexander Cox, @niklas_kluemper , and @Markuseckstein3 discuss these findings on UroToday! > @UniFAU @UniklinikBonn

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Niklas Klümper

@niklas_kluemper

5 months

Fantastic data of TRANSFORMER trial 💡: Sequential Bipolar androgen therapy (BAT)→ENZA could be a safe and effective third-line therapy for men with mCRPC progressing on abiraterone. Congrats to the authors 👏 @neerajaiims @OncoAlert @urotoday @JCO_ASCO @ASCOPost @DGUrologie

Neeraj Agarwal, MD, FASCO

@neerajaiims

3 years

Just in @JCO_ASCO 👉 Bipolar androgen Rx/BAT was as efficacious as enzalutamide after abiraterone in mCRPC #ProstateCancer . Fantastic collaboration including @huntsmancancer Great outcome with enza after BAT 👇 @EAntonarakis @sonpavde @OncoAlert @urotoday

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Niklas Klümper

@niklas_kluemper

4 months

Great study by @PTarantinoMD @DanaFarber on dynamic Her2 expression during NAT in breast cancer! Longitudinal analyses of ADC targets are key to developing the most rational therapeutic sequence given the growing ADC options (Her2, NECTIN4, TROP2, etc.) @OncoAlert @imedverse

Paolo Tarantino

@PTarantinoMD

4 months

In a large (≃1000) RW cohort from @DanaFarber , consistently with prior reports, we found that nearly 30% of breast tumors changed HER2 status after neoadjuvant treatment. This only impacted prognosis if HER2+➡️ HER2-neg. Our latest article now out on EJC.

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Niklas Klümper

@niklas_kluemper

2 months

Happy to share our beyond the abstract @urotoday on our manuscript about improving therapy monitoring in met. UC @EurUrolOncol Longitudinal assessment of simple inflammatory 🔥blood biomarkers (CRP + albumin integrated into modified Glasgow Prognostic Score/ mGPS) provides

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Niklas Klümper

@niklas_kluemper

4 months

Thanks for a great summary of @ASCO #GU24 Tom! @tompowles1 Longterm Response to Nivo+Ipi in mRCC is remarkable ➡️ 50% with ongoing response at 90month, 80% (53/66) with ongoing complete response in ITT 💪🏼 Anti-CTLA4 needed for durable response? @urotoday @OncoAlert @imedverse

Tom Powles

@tompowles1

4 months

Highlights #GU24 1) 38%⬆️ in OS for adjuvant pembro in RCC @DrChoueiri 2) ⬆️ DFS but no OS for adjuvant pembro in UC @apolo_andrea 3) ipi/nivo with ✅ long term data in IMDC good risk- Dr Tannir 4) olaparib and abi better together than alone on BRCA CRPC - Dr Hussian

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Niklas Klümper

@niklas_kluemper

2 months

Such a great trial design @MattGalsky !ctDNA guided adjuvant therapy (de)escalation is the way to go ! More biomarker-guided strategies are needed for met. UC as well, most importantly ADC precision oncology considering ADC target gene expression: NECTIN4 vs Her2 vs Trop2 ? 🎯

Matt Galsky

@MattGalsky

2 months

MODERN is open! Available at your site through the CRSU. Please help advance MRD-based adjuvant decision making in bladder cancer. @ALLIANCE_org @alantanmd @UroDocAsh @eaonc @SWOG @sonpavde @PaulCrispenMD @bergsa83 @SuzanneColeMD @NitinYerram @DrTylerStewart @DrRosenbergMSK

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Niklas Klümper

@niklas_kluemper

3 months

ADC target gene expression predicts ADC response and will be key for rational therapy sequencing/ combination 🚅 Best data is available for Her2 targeting ADC: clear correlation between Her2 status and response to T-DXd or disitamab vedotin 🎯 See DESTINY-PanTumor02 Phase II

Markus Eckstein

@Markuseckstein3

3 months

What do you think about surface target testing for antibody drug conjugates? 🏄‍♂️🎯 I personally believe it will be a future main task of predictive molecular pathology! Keen to hear your oppinion on this topic! @niklas_kluemper @urotoday @OncoAlert @shilpaonc @PGrivasMDPhD

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Niklas Klümper

@niklas_kluemper

2 years

Many thanks to the DGU and DFG! And in particular to Michael Hölzel, who is my mentor for the DFG Young Investigator Academy UroAgeCare! @HolzelMichael @IEO_HolzelLab @IEO_Bonn @ImmunoSens @UniBonn @dfg_public

Oliver Hahn

@hahnoliv

2 years

Thanks a lot to @dfg_public and @DGUrologie for an awesome kick-off workshop of the DFG Nachwuchsakademie UroAgeCare - lots of input, great talks! Thanks @chariskalogirou @niklas_kluemper @AnnemarieUhlig @petertessarz @HolzelMichael @ProfHadaschik @schmid_mariann @KuppeChristoph

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Niklas Klümper

@niklas_kluemper

3 months

Exciting data, SG + Pembro achieves ORR of 41% in mUC after platinum-based chemotherapy with mOS of 12,7 month! Congrats to @PGrivasMDPhD & @y_loriot ! ➡️But EV+Pembro achieves ORR >70% with mOS >30month; Cave: Cross-trial comparison and EV-302 was performed in previously

Markus Eckstein

@Markuseckstein3

3 months

Sacituzumab + Pembro is efficacious in metastic urothelial cancer following progress on platinum based chemotherapy !! Very interesting study by @PGrivasMDPhD and @y_loriot and team that unfortunately comes late. Is there still a place for this regimen after EV302 results ? But

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Niklas Klümper

@niklas_kluemper

11 months

Thanks @NatRevUrol for highlighting our work @JAMAOnc on longitudinal mGPS to improve response prediction in mRCC 🙏 @saal_jonas @Markuseckstein3 @ViktorGruenwald @HolzelMichael @IEO_Bonn @UniklinikBonn @urotoday @OncoAlert

Nature Reviews Urology

@NatRevUrol

11 months

A new research in @JAMANetwork shows that longitudinal measurement of systemic inflammatory response (through mGPS) in patients with mRCC provides valuable prognostic information and could integrate radiological staging in therapy monitoring

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Niklas Klümper

@niklas_kluemper

2 years

Thanks @EUplatinum for highlighting our work led by @Markuseckstein3 . Prediction of ICB response in UC is possible, but only in representative metastatic tissue not in archived primary tumors

European Urology

@EUplatinum

2 years

Spatial Immunephenotypes of Distant Metastases but not Matched Primary UC Predict Response to ICI Erlmeier, @Markuseckstein3 et al "MET immunephenotypes & MHC-I status show potential to predict chemo & durable ICI responses, while PRIM TIME does not"

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Niklas Klümper

@niklas_kluemper

1 year

Another exciting TROP-2 targeted ADC with promising clinical efficacy! Just published: First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of anti-TROP-2 Datopotamab Deruxtecan in Non–Small-Cell Lung Cancer: TROPION-PanTumor01 @ViktorGruenwald

First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface...

PURPOSE This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, and antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface...

ascopubs.org

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Niklas Klümper

@niklas_kluemper

2 years

mGPS outperforms the IMDC score in mRCC✔️! It is simple (mGPS: CRP + albumin vs. IMDC: 6 risk factors), investigator-independent, and can thus be easily incorporated into routine clinical practice. @Annals_Oncology @UniklinikBonn @IEO_HolzelLab Share link:

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Niklas Klümper

@niklas_kluemper

4 months

Great overview on UC pathology @Markuseckstein3 🔥 important to keep these pathways of UC carcinogenesis in mind for ADC targets as well, as NECTIN4 is overexpressed in luminal tumors as nicely demonstrated by @jonchou05 in @CCR_AACR @urotoday @OncoAlert

Heterogeneity in NECTIN4 Expression Across Molecular Subtypes of Urothelial Cancer Mediates...

Sensitivity to EV is mediated by expression of NECTIN4, which is enriched in luminal subtypes of bladder cancer. These findings may have implications for biomarker development, patient selection, and...

pubmed.ncbi.nlm.nih.gov

Markus Eckstein

@Markuseckstein3

4 months

In the first part we tried to understand the architecture of regular urothelium and key markers expressed in different layers of it. This important to understand why urothelial cancer can appear with multiple molecular and histological subtypes.

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Niklas Klümper

@niklas_kluemper

2 years

Congratulations, Michael! @HolzelMichael I am very happy for you and about being part of your group and the Institute of Experimental Oncology @IEO_HolzelLab @IEO_Bonn @ImmunoSens @UniBonn

Deutsche Krebshilfe

@Krebshilfe_Bonn

2 years

8,7 Millionen Euro für neues Exzellenzprogramm: Deutsche Krebshilfe fördert sechs Projekte mit hohem Innovationspotenzial ▶️

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Niklas Klümper

@niklas_kluemper

3 months

Great study @PTarantinoMD ! Tumors can develop ADC resistance by two main mechanisms: 1) Against the payload (eg TOP1 mut) or 2) restriction of membranous target gene expression! Similar patterns of resistance mechanisms have been observed for Trop2 targeting ADC SG in TNBC

Paolo Tarantino

@PTarantinoMD

3 months

Translational data on the activity of HER3-DXd for EGFR+ NSCLC. Comparing pre/post-ctDNA highlighted the emergence of a #TOP1 mutation (=resistance to the payload?) & an #ERBB3 mutation (=resistance to the mAb?). Much to unveil still on resistance to ADCs.

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Niklas Klümper

@niklas_kluemper

4 months

Great perspective from @FAndreMD & @BenjaminBesseMD @Nature : The community urgently needs to shift from using organ-based classifications of cancer to using molecular-based ones -> Tumor-agnostic targeted therapies (e.g. ADC) will be important for rapid implementation @OncoAlert

FabriceAndre

@FAndreMD

4 months

Metastatic cancers should be classified as much as possible based on their biology, and agnostic of organ of origin To reach this vision, new statistical tools are needed to claim that drugs work across multiple cancers TY @Nature & @lucy_os for the opportunity to write about it

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Niklas Klümper

@niklas_kluemper

6 months

@sonpavde @OncoAlert @practiceupdate @urotoday @PeerView @themednet @DrNeilLove Great overview of current UC trial landscape and future directions @sonpavde !

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Niklas Klümper

@niklas_kluemper

1 year

Great "Words of Wisdom" Response on 15-year ProtecT Update by @dr_coops at @EUplatinum . Clear Statement "For a case confirmed as low risk in contemporary practice including image guidance, there is essentially zero justification for immediate treatment"

Re: Fifteen-year Outcomes After Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Hamdy FC, Donovan JL, Lane JA, et al

www.europeanurology.com

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Niklas Klümper

@niklas_kluemper

1 year

We miss targetable genomic alterations when we analyze only the primary tumor in met. UC (e.g. 9% with FGFR3 mutation exclusive in metastasis). Further evidence to perform pre-treatment metastatic biopsy to guide targeted therapy decisions in met. UC @Markuseckstein3 @FaltasLab

Enrique Grande

@drenriquegrande

1 year

⚡️ Genomic heterogeneity as a barrier to precision oncology in urothelial cancer #bladdercancer @CellReports

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Niklas Klümper

@niklas_kluemper

8 months

Huge data for EV + Pembro in 1L met. UC. OS of 31,5m, HR 0.45 compared to Chemo. But do patients with low/ negative NECTIN4 expression benefit compared to Gem/ Cis plus Nivolumab (Ph3 CheckMate901) or Avelumab maintanance @OncoAlert @urotoday @ViktorGruenwald @Markuseckstein3

Toni Choueiri, MD

@DrChoueiri

8 months

The @myESMO LBAs are out And a wow for PEMBRO/EV (Presidential) OS 31.5 vs 16.1 months (HR 0.45) PFS 12.5 vs 6.3 months (HR 0.47) P<0.00001 A historic change for 1L mUC since Von Der Maase JCO 2000 @tompowles1 #ESMO23 @OncoAlert

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Niklas Klümper

@niklas_kluemper

6 months

Exciting to see another important validation of the tumor-agnostic potential of early CRP kinetics in predicting ICB response @jitcancer Dynamic biomarkers like CRP-flare 🔥or on-treatment mGPS are ready for prime time @JAMAOnc @OncoAlert @urotoday

Modified Glasgow Prognostic Score for Metastatic Renal Cell Carcinoma

This prognostic study assesses the prognostic and predictive value of the modified Glasgow prognostic score during treatment in patients with metastatic renal cell carcinoma.

jamanetwork.com

Journal for ImmunoTherapy of Cancer

@jitcancer

6 months

New #JITC article: Early kinetics of C reactive protein for cancer-agnostic prediction of therapy response and mortality in patients treated with immune checkpoint inhibitors: a multicenter cohort study

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Niklas Klümper

@niklas_kluemper

8 months

@HolzelMichael @IEO_Bonn @UniklinikBonn @dgukongress @DGUrologie @UniBonn @BMBF_Bund I am very grateful for your incredible support and guidance @HolzelMichael 🙏 #Mentorship "

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Niklas Klümper

@niklas_kluemper

4 months

Insightful paper on the immunomodulatory effect of cisplatin vs. carboplatin in UC 🔎 @MattGalsky Explanation why Gem/Cis + Nivo (Ph3 CheckMate901 @NEJM ) was positive? UC is often immunogenic🔥but can also get inflamed via chemo! @Markuseckstein3 @OncoAlert @urotoday @imedverse

Cell Reports Medicine

@CellRepMed

4 months

Online now: Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus atezolizumab in urothelial cancer

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Niklas Klümper

@niklas_kluemper

1 year

Chance for ADC precision oncology to select a particular ADC based on target expression (e.g., Trop2 vs. NECTIN-4)? @ViktorGruenwald @Markuseckstein3 @HolzelMichael @IEO_Bonn @drenriquegrande @JoshMeeks @apolo_andrea @CChuMD @Dr_Aggen @DrRosenbergMSK

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Niklas Klümper

@niklas_kluemper

7 months

Thanks @urotoday for highlighting our work: Integration of on-treatment mGPS (based on CRP and albumin) to improve therapy monitoring in addition to radiologic staging for mRCC. Additive prognostic information for large and heterogeneous subgroup with SD @JAMAOnc @OncoAlert

UroToday.com

@urotoday

7 months

Integrating on-treatment modified Glasgow prognostic score and imaging to predict response and outcomes in metastatic #RenalCellCarcinoma . #BeyondTheAbstract with @niklas_kluemper @UniklinikBonn > @JAMAOnc

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Niklas Klümper

@niklas_kluemper

1 year

Big thanks to @Dr_Aggen @CChuMD and @DrRosenbergMSK for their great comment on our work on NECTIN-4 expression to predict response to Enfortumab vedotin in patients with met. UC @Markuseckstein3 @CCR_AACR . Please also see our tweetorial on that topic:

David H Aggen, MD PhD

@Dr_Aggen

1 year

Out in CCR, Klümper et al illustrate differential nectin-4 expression in paired primary and metastatic samples. Commentary in CCR now with @CChuMD @DrRosenbergMSK here

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Niklas Klümper

@niklas_kluemper

2 months

Absolutely agree to this statement: High-quality biospecimens should be assembled regularly within clinical trials for future research and especially biomarker development! Would be an important step to develop biomarkers to predict response or resistance for precision oncology

Parminder singh

@Parminder1699

2 months

Elise Kohn talking about how to access bio specimens from Co-op studies. Great session chaired by Josh Meeks @JoshMeeks @PGrivasMDPhD @montypal @slernerbcmedu1 @djmcconkey

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Niklas Klümper

@niklas_kluemper

2 years

Thanks @Annals_Oncology for highlighting our work: The modified Glasgow prognostic score outperforms the IMDC score, which is the current clinical standard for risk stratification and impacts 1L treatment decisions in metastatic RCC! @saal_jonas @IEO_HolzelLab @IEO_Bonn @UniBonn

Annals of Oncology

@Annals_Oncology

2 years

The IMDC score is used for risk stratification in the 1st line treatment of mRCC. The mGPS, based on baseline CRP + albumin levels, was tested on data from the IMmotion151 ph3 clinical trial. Results 👇 @saal_jonas @niklas_kluemper @IEO_Bonn @UniBonn

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Niklas Klümper

@niklas_kluemper

2 years

Exciting study on an early on-treatment biomarker for predicting immunotherapy response in NSCLC. Dynamic inflammatory biomarkers such as CRP flare concept 🔥() capture complex tumor-immune interactions and push to the clinics. @IEO_baldlab @IEO_HolzelLab

C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung...

Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a...

jitc.bmj.com

Journal for ImmunoTherapy of Cancer

@jitcancer

2 years

New #JITC article: Longitudinal plasma proteomic profiling of patients with non-small cell lung cancer undergoing immune checkpoint blockade @ShakedYuval @APDicker

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Niklas Klümper

@niklas_kluemper

1 year

@Markuseckstein3 @drenriquegrande @tompowles1 @PGrivasMDPhD @montypal @apolo_andrea @shilpaonc @sonpavde @OncoBellmunt @MattGalsky @cdanicas @DrYukselUrun @CChuMD @HolzelMichael We have also summarized the data of our open access @CCR_AACR in a tweetorial: …. We are very excited about the feedback from the uro-oncology community ! @Markuseckstein3 @damian_ralser @HolzelMichael @IEO_Bonn

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcin...

AbstractPurpose:. The antibody–drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients...

aacrjournals.org

Niklas Klümper

@niklas_kluemper

1 year

Happy to share our work: Membranous NECTIN-4 expression frequently decreases during metastatic spread of urothelial carcinoma and is associated with enfortumab vedotin resistance @CCR_AACR Follow our tweetorial about this clinically important data 1/12

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Niklas Klümper

@niklas_kluemper

4 months

E.g. Her2-ADC and FOLR1-ADC are currently approved based on target antigen expression in solid tumors 🎯 Membranous NECTIN-4 correlates with EV response as well, but is not considered ➡️ Why? Biomarkers to optimize use of EV needed! 💪🏼 @oncoalert @urotoday @imedverse @uromigos

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Niklas Klümper

@niklas_kluemper

2 years

Thanks @sonpavde for highlighting our work on the predictive potential of CRP flare in mUC🔥! Early and cost-efficient on-treatment biomarker to optimize ICB monitoring across entities - recently also shown for NSCLC (PMID: 35292517). @Markuseckstein3 @IEO_HolzelLab @Doc_Bald

Guru P. Sonpavde, MD

@sonpavde

2 years

CRP flare predicts response to anti–PD-L1 #immunotherapy in Metastatic #urothelialcarcinoma -early dynamics of NLR (neutrophil/lymphocyte ratio) promising too-affordable non-invasive markers-but no commercial incentives unlike #ctDNA @practiceupdate

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Niklas Klümper

@niklas_kluemper

4 months

@scserendipity1 @JCO_ASCO @PTarantinoMD @ASCO @urotoday @OncoAlert @imedverse @Markuseckstein3 Thanks @scserendipity1 We and others () believe yes: Membranous NECTIN4 expression is correlated to EV response. Further, app. 40% of oUC metastatic samples are lacking membranous NECTIN4

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcin...

AbstractPurpose:. The antibody–drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients...

aacrjournals.org

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Niklas Klümper

@niklas_kluemper

3 months

Super interesting paper in @JCO_ASCO delves into the mechanisms of immunotherapy resistance. Immunophenotyping reveals intriguing shifts in intratumoral lymphocytes, CD8a+ T cells, PD-L1–PD1 engagement, as well as increased distance between tumor cells and CD8+PD-1+ T cells. A

Journal of Clinical Oncology

@JCO_ASCO

3 months

🧐 #JCO #BiologyOfNeoplasia : Genomic and immunophenotypic changes shape acquired resistance to #ICI in #NSCLC : @BiagioRicciutMD @GLambertiMD @DanaFarber #LCSM

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Niklas Klümper

@niklas_kluemper

11 months

@Applied_Rad Thanks for highlighting our work @Applied_Rad @JAMAOnc !

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Niklas Klümper

@niklas_kluemper

9 months

T-DXd receives approval for HER2+ solid tumors based on DESTINY-PanTumor02. T-DXd with 56.3% ORR in HER2 IHC 3+ met. UC 🎯Big step towards 1st tumor agnostic approval. ADC precision oncology´s future is looking bright!💡 @Markuseckstein3 @ViktorGruenwald @PTarantinoMD

Paolo Tarantino

@PTarantinoMD

9 months

T-DXd granted breakthrough therapy designation by the FDA for the treatment of HER2-expressing (IHC 3+) solid tumors, based on the results of DESTINY-PanTumor02. One step closer to the approval of the first histology agnostic ADC.

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Niklas Klümper

@niklas_kluemper

9 months

App, 25% of cases show divergent FGFR3 status between primary and metastatic samples in mUC. Heterogeneity during metastatic spread in membranous NECTIN-4 IHC further highlights the need for metastatic biopsies in #UC patients for precision oncology 🎯 @Markuseckstein3 @urotoday

Brendan Guercio

@BrendanGuercio

9 months

Delighted to share the @MSKCancerCenter experience in FGFR-altered #BladderCancer now in @CCR_AACR . FGFR2/3 are crucial oncodrivers in multiple cancers and currently the only genomic alteration with an FDA-approved therapy in #BladderCancer , #erdafitinib

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