First-in-human data for potential first-in-class anti-CEACAM5 ADC with topoisomerase 1 inhibitor payload, M9140, in treatment of metastatic colorectal cancer to be featured in oral presentation
Phase I data for tuvusertib, lead asset from the company’s unique portfolio of DDR inhibitors, including an oral presentation on the combination with a PARP inhibitor, support further clinical development
New analyses contribute to totality of evidence supporting BAVENCIO first-line maintenance as a standard-of-care in advanced bladder cancer
Not intended for Canada-, UK- or US-based media
DARMSTADT, Germany--(BUSINESS WIRE)--Merck, a leading science and technology company, today announced new research from the company’s diverse oncology portfolio will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31 to June 4, Chicago. Data from company- and investigator-sponsored studies include 31 accepted abstracts across more than 10 tumor types, including seven oral presentations, highlighting the company’s innovative oncology pipeline encompassing potential first-in-class approaches designed to hit cancer at its core.
“Our research at the 2024 ASCO Annual Meeting showcases the advancement of our novel pipeline designed to exploit the major vulnerabilities of cancer, with new data from our lead investigational antibody-drug conjugate and our DNA damage response portfolio,” said Victoria Zazulina, M.D., Head of Development Unit, Oncology, for the Healthcare business of Merck. “In addition, new analyses from pivotal studies and collaborations underline our determination to maximize the impact of our standard-of-care treatments as we seek to improve the lives of those living with cancer.”
Highlights of the company’s data include:
First-in-human data for the antibody-drug conjugate (ADC) M9140 (Abstract 3000). This Phase I trial is investigating the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of M9140, the company’s investigational ADC against carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) with a novel exatecan payload, in heavily pretreated patients with metastatic colorectal cancer. Data from 40 patients treated across seven dose levels in Part 1A of the study showed encouraging clinical activity and a manageable and predictable safety profile in this population. The randomized dose-expansion part of the study is ongoing.
New findings for tuvusertib, the lead oral ATRi asset from the company’s portfolio of DNA damage response (DDR) inhibitors (Abstracts 3018, 2612, 2614). Data from the DDRiver™ Clinical Trials program highlight the potential of the investigational oral ataxia telangiectasia and RAD3-related inhibitor (ATRi) tuvusertib in various combinations across solid tumors.
- Part B1 of the Phase I DDRiver Solid Tumors 301 study assessed safety as well as PK, pharmacodynamics, and preliminary efficacy of different dosing regimens of tuvusertib in combination with the poly-ADP ribose polymerase (PARP) inhibitor niraparib in patients with locally advanced or metastatic unresectable solid tumors refractory to standard treatment. Data show a manageable safety profile and preliminary efficacy in patients with advanced solid tumors, confirming suitability of this combination for further evaluation.
- Presentations from the Phase Ib DDRiver Solid Tumors 320 study showcase further data on the combination of tuvusertib with the company’s ataxia telangiectasia-mutated (ATM) inhibitor lartesertib, building on the safety and efficacy data presented at the AACR Annual Meeting in April 2024, and for the first time, with the company’s immune checkpoint inhibitor BAVENCIO® (avelumab). The findings further support that both DDRi assets are well-positioned for combination development building on in-house expertise.
Post-hoc independent read confirmation of Phase II efficacy data for xevinapant (Abstract e18039). A previously published Phase II study of the investigational oral IAP (inhibitor of apoptosis protein) inhibitor xevinapant plus chemoradiotherapy (CRT) versus placebo plus CRT in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) showed improved efficacy outcomes. This post-hoc analysis showed consistent outcomes when comparing the review of selected efficacy endpoints by blinded independent review committee (BIRC) with previously reported outcomes by investigator review. Xevinapant plus CRT demonstrated a 62% reduction in the risk of disease progression (by BIRC) or death compared with placebo plus CRT, with prolonged duration of response and increased complete response rates.
Long-term efficacy and safety analyses from JAVELIN Bladder 100 (Abstracts 4566, 4567). New analyses of this Phase III study, which has previously shown in a post-hoc exploratory analysis a median overall survival of 29.7 months in patients who received BAVENCIO plus best supportive care (BSC) as measured from the start of first-line chemotherapy, confirm the benefit of BAVENCIO first-line maintenance in key subgroups of patients with advanced urothelial carcinoma that has not progressed on platinum-based chemotherapy, including those who have low tumor burden and in those with mixed histologic subtypes. These findings further support the use of the JAVELIN Bladder regimen as a standard of care in this setting and as an important first-line treatment regimen for patients with low tumor burden in particular, where pronounced efficacy with BAVENCIO (vs BSC alone) was observed.
Health-related quality-of-life data for TEPMETKO® (tepotinib) in NSCLC (Abstract 8575). This analysis reports health-related quality of life (HRQoL) outcomes from the Phase II VISION study of TEPMETKO in patients with metastatic non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations with brain, liver, adrenal or bone metastases. These patients experienced stable HRQoL during treatment with TEPMETKO, with trends for improvement in cough, consistent with results for the overall population.
Additional company-sponsored activity at ASCO:
Medical Evening Lecture
What's new in LA SCCHN? An evasive enemy and an evolving landscape
Faculty: Kevin Harrington (chair), Institute of Cancer Research, UK; Ari Rosenberg, University of Chicago Medicine, USA; Jonathan Schoenfeld, Dana-Farber Cancer Institute, USA; Sue Yom, University of California, San Francisco, USA
June 2, 2024, 7:00PM-8:00PM CDT
W Chicago City Center hotel (172 West Adams Street), Great Room I
Select Merck-related abstracts accepted for the ASCO 2024 Annual Meeting include (all times in CDT):
|
Title |
Lead Author |
Abstract |
Session Information |
|
M9140 |
|
|
|
|
First-in-human trial of M9140, an anti-CEACAM5 antibody-drug conjugate (ADC) with exatecan payload, in patients with metastatic colorectal cancer. |
Kopetz, S |
3000 |
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, HALL D1 Date: Saturday June 1, 2024 Session Time: 3:00-6:00PM Presentation Time: 3:00-3:06PM Location: Hall D1 |
|
DDRi |
|
|
|
|
A phase I study of highly potent oral ATR inhibitor tuvusertib plus oral PARP inhibitor niraparib in patients with solid tumors. |
Yap, T |
3018 |
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Date: Monday June 3, 2024 Session Time: 8:00 -9:30AM Presentation Time: 9:00-9:12AM Location: S406 |
|
Pharmacodynamic and immunophenotyping analyses of ATR inhibitor tuvusertib + ATM inhibitor lartesertib in a phase Ib study in patients with advanced unresectable solid tumors. |
Boni, V |
2612 |
Session Title: Developmental Therapeutics—Immunotherapy Date: Saturday June 1, 2024 Session Time: 9:00AM-12:00PM Location: Hall A |
|
Pharmacokinetic and pharmacodynamic findings from a phase 1b study of ATR inhibitor tuvusertib + anti-PD-L1 avelumab in patients with advanced unresectable solid tumors. |
Tolcher, A |
2614 |
Session Title: Developmental Therapeutics—Immunotherapy Date: Saturday June 1, 2024 Session Time: 9:00AM-12:00PM Location: Hall A |
|
Xevinapant |
|
|
|
|
Phase 2 study of xevinapant + chemoradiotherapy (CRT) vs placebo + CRT in patients with unresected locally advanced squamous cell carcinoma of the head and neck: A post hoc activity analysis by blinded independent review committee evaluation. |
Bourhis, J |
e18039 |
Accepted for e-publication |
|
Xevinapant with radiation and concurrent carboplatin and paclitaxel in patients ineligible for cisplatin with locoregionally advanced squamous cell carcinoma of the head and neck (The EXtRaCT study) |
Mir, NA |
TPS6126 |
Session Title: Head and Neck Cancer Date: Sunday June 2, 2024 Session Time: 9:00AM-12:00PM Location: Hall A |
|
BAVENCIO (avelumab) |
|||
|
Avelumab first-line maintenance for advanced urothelial carcinoma: Long-term outcomes from JAVELIN Bladder 100 in patients with low tumor burden. |
Bellmunt, J |
4566 |
Session Title: Genitourinary Cancer—Kidney and Bladder Date: Sunday June 2, 2024 Session Time: 9:00AM-12:00PM Location: Hall A |
|
Avelumab first-line maintenance for advanced urothelial carcinoma: Long-term outcomes from the JAVELIN Bladder 100 trial in patients with histological subtypes. |
Loriot, Y |
4567 |
Session Title: Genitourinary Cancer—Kidney and Bladder Date: Sunday June 2, 2024 Session Time: 9:00AM-12:00PM Location: Hall A |
|
Avelumab + axitinib vs sunitinib in patients with advanced renal cell carcinoma: Final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial. |
Motzer, R |
4508 |
Session Title: Genitourinary Cancer—Kidney and Bladder Date: Monday June 3, 2024 Session Time: 8:00-11:00AM Presentation Time: 10:12-10:24AM Location: Hall B1 |
|
ERBITUX (cetuximab) |
|
|
|
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Efficacy of FOLFIRI plus bevacizumab versus FOLFIRI plus cetuximab in RAS-mutant metastatic colorectal cancer: Final update on RAS mutant patients treated in FIRE-3. |
Weiss, L |
3550 |
Session Title: Gastrointestinal Cancer—Colorectal and Anal Date: Saturday June 1, 2024 Session Time: 1:30-4:30PM Location: Hall A |
|
Encorafenib and cetuximab versus irinotecan/cetuximab or FOLFIRI/cetuximab in Chinese patients with BRAF V600E mutant metastatic colorectal cancer: The NAUTICAL CRC study. |
Wang, X |
LBA3559 |
Session Title: Gastrointestinal Cancer—Colorectal and Anal Date: Saturday June 1, 2024 Session Time: 1:30-4:30PM Location: Hall A |
|
TEPMETKO (tepotinib) |
|
|
|
|
Health-related quality of life with tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer with brain, liver, adrenal, or bone metastases in the phase II VISION trial. |
Reinmuth, N |
8575 |
Session Title: Lung Cancer—Non-Small Cell Metastatic Date: Monday June 3, 2024 Session Time: 1:30 -4:30PM Location: Hall A |
