pamvatamig (MCLA-129) / Merus, Betta Pharma - LARVOL DELTA

Correlation between MET amplification/overexpression status and response to MCLA-129 in advanced non-small-cell lung cancer (NSCLC): biomarker results from a phase 1 trial (AACR 2025) - P1/2 | "MCLA-129 showed clinically meaningful antitumor activity in advanced NSCLC with MET OE or METamp, particularly in pts with concurrent mutations. High GCN seemed to be associated with better efficacy in MET-amplified advanced NSCLC, suggesting its predictive properties.GCN cut-offNORR, % (95% CI)≥31546.7 (21.3-73.4)≥41060.0 (26.2-87.8)≥5771.4 (29.0-96.3)≥6666.7 (22.3-95.7)≥72100 (15.8-100)"

Biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Study of MCLA-129 in the Treatment of Advanced Non-small Cell Lung Cancer with AGA and MET Amplification. (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

SCS04: Lung Cancer Tumor Board®: Mastering Advances in Managing Unresectable and Metastatic NSCLC—Immunotherapy, Targeted Therapies, and Emerging Strategies (IASLC-TTLC 2025) - "Trials such as TROPION-Lung05 and TROPION-Lung15 have showcased the efficacy of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with osimertinib, offering promising therapeutic options for patients who have progressed on prior EGFR inhibitors. Concurrently, the use of bispecific antibodies such as MCLA-129, targeting both EGFR and MET, exemplifies the expanding role of dual-targeted therapies in addressing complex resistance profiles...Trials such as PACIFIC and PACIFIC-R have established durvalumab as a cornerstone of consolidation therapy following concurrent chemoradiotherapy (CRT), while ongoing studies like PACIFIC-9 and KEYLYNK-012 explore combination strategies to enhance outcomes. For patients with advanced or metastatic disease, the combination of osimertinib and chemotherapy, validated in the FLAURA2 trial, marks a significant step forward, improving both progression-free survival and central nervous system (CNS) control. This educational..."

IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors (clinicaltrials.gov) - P1/2 | N=400 | Recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd. | Trial completion date: Jun 2025 ➔ Dec 2028 | Trial primary completion date: Jun 2024 ➔ Apr 2028

Trial completion date • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Merus Announces Financial Results for the Third Quarter 2024 and Provides Business Update (GlobeNewswire) - "Investigation of MCLA-129 is ongoing in METex14 NSCLC; phase 2 trial in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC enrolling...In the third quarter, Merus announced the first patients were dosed in the phase 2 trial evaluating MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC, with a cohort receiving MCLA-129 and paclitaxel and carboplatin, and another cohort receiving MCLA-129 and docetaxel. We also remain interested in partnering MCLA-129 to sufficiently resource the development of MCLA-129 and the potential benefit it may have for patients."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Beida Pharmaceuticals (300558.SZ): Clinical trial application for injection of MCLA-129 for the treatment of advanced solid tumors accepted [Google translation] (Zhitong Finance) - "According to the Zhitong Finance APP, Beida Pharmaceutical...announced that the company's clinical trial application for MCLA-129 injection developed by the company has received the 'Acceptance Notice' issued by the National Medical Products Administration ('NMPA'). The indication of this application is intended for 'advanced solid tumors (including but not limited to wild-type colorectal cancer, liver cancer, head and neck squamous cell carcinoma, pancreatic cancer, adenocarcinoma of unknown primary and squamous cell carcinoma and other advanced solid tumors)'."

New trial • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

METex14: Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR, Anti-c-MET Bispecific Antibody, in Advanced NSCLC and Other Solid Tumors, Alone and in Combination (clinicaltrials.gov) - P1/2 | N=576 | Recruiting | Sponsor: Merus N.V. | N=380 ➔ 576 | Trial completion date: Apr 2025 ➔ Mar 2027 | Trial primary completion date: Apr 2024 ➔ Mar 2026

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Efficacy and safety of MCLA-129, an EGFR/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC). (ASCO 2024) - P1/2 | "MCLA-129 demonstrates robust and durable antitumor activity in patients with NSCLC harboring METex14, EGFR exon20ins and sensitized EGFR mutations, with a manageable safety profile; enrollment in dose expansion is ongoing."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in non-small-cell lung cancer (NSCLC) with c-MET exon 14 skipping mutations (METex14). (ASCO 2024) - P1/2 | "Significant tumor shrinkage was observed in one patient with METex14 NSCLC previously treated with multiple chemotherapy agents and the c-MET tyrosine kinase inhibitor (TKI) capmatinib. MCLA-129 is being evaluated as monotherapy for the treatment of patients with locally advanced/metastatic c-MET exon 14 skipping NSCLC."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Merus’ MCLA-129 Demonstrates Promising Single-Agent Efficiency in METex14 NSCLC in Poster Presentation at the 2024 ASCO Annual Meeting (GlobeNewswire) - P1/2 | N=360 | NCT03526835 | Sponsor: Merus N.V. | "Merus...announced the publication of a poster regarding MCLA-129 presented at the 2024...ASCO Annual Meeting....As of a February 16, 2024 data cutoff date, 22 patients (pts) were treated and 14 pts (64%) were continuing treatment....15 pts were evaluable for response having received ≥2 treatment cycles, measurable disease at baseline and ≥1 post-baseline scan. Response rate overall: 3 partial responses (PRs) and 6 unconfirmed PRs (uPRs) were observed by Response Evaluation Criteria in Solid Tumors v1.1 per investigator assessment; 5 of the 6 uPRs were confirmed and 1 uPR progressed after the data cutoff (8/15 confirmed PRs [53%]). 6 of 8 TKI-naïve cancers responded, one of which was an initial uPR that progressed after data cutoff."

P1/2 data • Non Small Cell Lung Cancer

Merus Announces Publication of Abstracts for Presentation at the 2024 ASCO Annual Meeting (GlobeNewswire) - P1 | N=118 | NCT03922204 | Sponsor: Merus N.V. | "Merus N.V...announced the publication of an abstract regarding MCLA-145 and an abstract regarding MCLA-129 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago May 31-June 4, 2024....5 partial responses (PRs) were observed in a variety of tumor types including: glioblastoma (ongoing>3 years), sarcoma, cervical, anal, and gastric cancer (treated for 2-11 month (mo)) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment. Combination: 19 pts were treated with MCLA-145 10, 25 or 40 mg plus pembrolizumab Q3W: The RDE was established at 40 mg Q3W."

P1 data • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Merus Announces Financial Results for the First Quarter 2024 and Provides Business Update (GlobeNewswire) - "In 2024, Merus is planning to initiate the evaluation of petosemtamab with standard chemotherapy in 2L CRC....MCLA-129 in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC planned to start in 2024."

New trial • Colorectal Cancer • Non Small Cell Lung Cancer

Merus Announces Abstracts Accepted for Presentation at the 2024 ASCO Annual Meeting (GlobeNewswire) - "Merus...announced the acceptance of three abstracts for presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....Petosemtamab in combination with pembrolizumab in 1L HNSCC initial interim clinical data selected for rapid oral session presentation. MCLA-145 as monotherapy or in combination with pembrolizumab in solid tumors initial interim clinical data selected for rapid oral session presentation. MCLA-129 in NSCLC with c-MET exon 14 skipping mutations initial interim clinical data selected for poster presentation."

Clinical data • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Merus Announces Financial Results for the Fourth Quarter and Full Year 2023 and Provides Business Update (GlobeNewswire) - "MCLA-129: MCLA-129 is in clinical development in a phase 1/2, open-label clinical trial evaluating MCLA-129 monotherapy in patients with MET ex14 NSCLC and Merus plans to start a cohort of MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC in 2024."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in head and neck squamous cell cancer (HNSCC) (ESMO Asia 2023) - P1/2 | "Pts received a median of 2 lines of prior systemic therapy, including anti-PD-(L)1 (78%) and platinum-based chemotherapy (89%); 28% received cetuximab in the RM setting. No cases of interstitial lung disease were reported in this cohort. Conclusions MCLA-129 monotherapy demonstrated antitumor activity in pts with pretreated RM HNSCC with a manageable safety profile."

Clinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MET

Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC) (ESMO Asia 2023) - P1/2 | "Conclusions MCLA-129 plus osimertinib showed promising clinical efficacy in EGFRmut NSCLC, in 1L and 2L+. IRRs and ILD/pneumonitis were observed."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Merus Presents Interim Data on MCLA-129 at ESMO Asia Congress 2023 (GlobeNewswire) - P1/2 | N=380 | NCT04868877 | Sponsor: Merus N.V. | "Merus...announced updated interim clinical data on MCLA-129 from ongoing expansion cohorts...in previously treated head and neck squamous cell carcinoma (HNSCC) were presented at the European Society for Medical Oncology (ESMO) Asia Congress 2023....As of an August 10, 2023 data cutoff date, 22 pts with previously treated HNSCC were treated: 20 pts were evaluable for response; Pts received a median of 3 lines of prior therapy, 22% prior chemotherapy, 20% prior anti-PD-(L) 1, 36% prior cetuximab; 1 confirmed and 1 unconfirmed PR were observed (2/20, 10%, 95% CI 1–32) by RECIST v1.1. per investigator assessment; The confirmed response was ongoing with a duration of response of 3.4+ months at data cutoff date; The unconfirmed PR was confirmed after the data cutoff date with treatment still ongoing at the time of presentation."

P1/2 data • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Merus Presents Interim Data on MCLA-129 at ESMO Asia Congress 2023 (GlobeNewswire) - P1/2 | N=380 | NCT04868877 | Sponsor: Merus N.V. |"Merus...announced updated interim clinical data on MCLA-129 from ongoing expansion cohorts in NSCLC...were presented at the European Society for Medical Oncology (ESMO) Asia Congress 2023....In the 1L setting, 16 pts were treated, with all pts evaluable for response: All 16 pts experienced tumor shrinkage; 9 confirmed partial responses (PRs) and 3 unconfirmed PRs were observed (12/16, 75%; 95% CI 48-93) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment; 11 responses were ongoing, including the 3 unconfirmed PRs....In the 2L+ setting, 44 pts were treated, with 34 pts evaluable for response:...11 confirmed PRs and 1 unconfirmed PR were observed (12/34, 35%; 95% CI 20-54) by RECIST v1.1. per investigator assessment, 9 responses were ongoing as of the data cutoff date, including the 1 unconfirmed PR....MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC planned to initiate 1Q24."

P1/2 data • Trial status • Non Small Cell Lung Cancer

Merus Announces Publication of Abstracts on MCLA-129 for Presentation at ESMO Asia Congress 2023 (GlobeNewswire) - P1/2 | N=380 | NCT04868877 | Sponsor: Merus N.V. | "Efficacy and safety of MCLA-129...in head and neck squamous cell cancer (HNSCC) Observations in the abstract include: As of a May 10, 2023 data cutoff date, 18 pts with previously treated HNSCC were treated. 12 pts were evaluable for response. 2 unconfirmed PRs were observed (2/12, 17%) by RECIST v1.1. per investigator assessment; one response was ongoing as of the data cutoff date...Most common AEs regardless of causality were IRRs (composite term) in 72% (28% ≥ G3), all on cycle 1 day 1, that led to treatment discontinuation in two pts."

P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Merus Announces Publication of Abstracts on MCLA-129 for Presentation at ESMO Asia Congress 2023 (GlobeNewswire) - P1/2 | N=380 | NCT04868877 | Sponsor: Merus N.V. | "Efficacy and safety of MCLA-129...as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC) Observations in the abstract include: 2 confirmed partial responses (PRs) and 6 unconfirmed PRs were observed (8/10, 80%; 95% CI 44-98) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment; all responses were ongoing as of the data cutoff date; 90% disease control rate (DCR) (95% CI 56-100); 6 confirmed PRs and 5 unconfirmed PRs were observed (11/22, 50%; 95% CI 28-72) by RECIST v1.1. per investigator assessment; 9 responses were ongoing as of the data cutoff date, including 4 of the unconfirmed PRs."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Merus announces conference call to provide an update on its activities [Google translation] (GlobeNewswire) - "Abstracts on bispecific antibody MCLA-129 in NSCLC and previously treated CCSTC have been selected for presentation at the ESMO Asia Congress 2023 in Singapore from December 1-3 2023....Merus is discontinuing the EGFR exon20 mutated NSCLC cohort due to competition in this niche market."

P1/2 data • Trial status • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Merus Announces Abstracts Accepted for Presentation at the ESMO Asia Congress 2023 (GlobeNewswire) - "Merus N.V...today announced the acceptance of abstracts on the bispecific antibody MCLA-129 in non-small cell lung cancer (NSCLC) and in previously treated head and neck squamous cell carcinoma (HNSCC) for presentation at the European Society for Medical Oncology Congress (ESMO) Asia Congress 2023 taking place in Singapore December 1-3, 2023....MCLA-129 is in clinical development in a phase 1/2, open-label clinical trial evaluating MCLA-129 monotherapy in patients with MET ex14 NSCLC, and in HNSCC, as well as MCLA-129 in combination with osimertinib, a third generation EGFR TKI, in patients with treatment-naïve EGFR mutant (m) NSCLC and in patients with EGFRm NSCLC that have progressed on osimertinib. Merus has discontinued enrollment in the exon20 NSCLC cohort due to competitive reasons."

Enrollment status • P1/2 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR • Exon 20

Study of MCLA-129 Combined With Befotertinib in the Treatment of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation (clinicaltrials.gov) - P1 | N=172 | Not yet recruiting | Sponsor: Betta Pharmaceuticals Co., Ltd.

Metastases • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Betta Pharmaceuticals: The clinical trial application for the combination of MCLA-129 Injection for Injection and Befutinib Mesylate Capsules has been accepted (Daily Economic News - NBD) - "Betta Pharmaceuticals announced on May 10 that the drug clinical trial application for the combination of MCLA129 for injection and Befatinib Mesylate Capsules declared by the company has been accepted by the State Food and Drug Administration. The clinical trial application of MCLA-129 combined with befotinib mesylate is intended for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 (L858R) substitution mutation."

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preclinical evaluation of MCLA-129, a bispecific antibody targeting EGFR and c-MET on solid tumor cells, in comparison with amivantamab (AACR 2023) - "A phase 1/2 clinical trial of MCLA-129 in solid tumors is ongoing. These data support the further clinical development of MCLA-129 in patients with NSCLC and other solid tumors."

Preclinical • Tumor cell • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET