CMG901 Demonstrates Favorable Safety/Tolerability in Advanced Solid Tumors

In patients with advanced solid tumors, CMG901 was well-tolerated and showed a favorable safety profile, according to findings from the KYM901 phase 1a dose-escalation trial of the agent (NCT04805307).¹

The novel drug candidate, CMG901, is a Claudin 18.2 antibody drug conjugate made up of an anti-Claudin 18.2 monoclonal antibody, a protease-degradable linker, and a cytotoxic small molecule monomethyl auristatin. The agent has been approved for clinical trials in the United States and China.

In this phase 1a trial, preliminary efficacy data showed that in patients with 8 Claudin 18.2-positive gastric/gastroesophageal junction adenocarcinoma (GEJ) cancer receiving CMG901, the objective response rate (ORR) was 75%, the disease control rate (DCR) was 100%, and the ORR was 100% in the 2.6, 3.0, and 3.4 mg/kg cohorts, respectively. Median progression free survival (PFS) and median overall survival (OS) were not reached yet.

The agent also demonstrated a favorable safety and tolerability profile as CMG901 at doses of ≥1.8 mg/kg led to encouraging anti-tumor activity in patients with Claudin 18.2-positive gastric/GEJ cancers.

Grade 3 or greater adverse events (AEs) were observed in 3 of 27 (11.1%) patients and no drug-related grade 4 or greater AEs were reported. Patients were given CMG901 at dose levels up to 3.4 mg/kg, but the maximum tolerated dose (MTD) of the agent was not reached. Further, 1 patient in the 2.2 mg/kg cohort of the trial developed a dose-limiting toxicity (DLT).

Full results of the trial will be presented in a poster at the 2023 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology.

In this first-in-human phase I trial, investigators are evaluating CMG901 in patients with advanced solid tumors who had failed to respond to standard of care or had no available standard of care regimen. The goal of the trial is to determine the safety, tolerability,

pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of KYM901.²

The study comprises a modified dose escalation part (phase 1a) and dose-expansion part (phase 1b). In phase 1a, investigators will determine the MTD of CMG901 and patients are not required to be positive for Claudin 18.2 expression. However, Claudin 18.2 positivity tested by the central lab is required for patients to be entered into the phase 1b portion of trial. This portion of the trial will evaluate the preliminary anti-tumor activity and safety of CMG901.

A total of 27 patients, including 13 patients with gastric/GEJ cancer and 14 patients with pancreatic cancer, were enrolled in the phase 1a portion of the clinical study. Patients were required to have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies which does not have standard treatment or effective treatment, must have provided archival tumor tissue specimen, or agree to undergo a fresh biopsy, and have measurable or evaluable disease per RECIST v 1.1.

In part 2 of the study, patients must have histologically-confirmed, advanced unresectable or metastatic gastric/GEJ adenocarcinoma or pancreatic cancer, provide a CLDN18.2-positive tumor sample assessed by central testing, and measurable disease per RECIST v 1.1. For both portions of the study, patients must also have an ECOG performance status of 0-1 and have recovered from AEs to grade 0 or 1.

Primary end points of the study are the number of patients with a DLT and AEs for part 1a, and ORR and recommended phase 2 dose for part 2b. For the first portion, investigators will also assess the secondary end points of Claudin 18.2 expression by retrospective testing in tumor specimens by immunohistochemistry, ORR, OS, and AEs, and for both parts of the trial, secondary end points include pharmacokinetics, incidence of anti-CMG901, DCR, DOR, and PFS.

REFERENCES:

Keymed Biosciences | The latest results from the phase 1a clinical study of CMG901 was presented at the 2023 ASCO gi cancers symposium. News release. Keymed Biosciences, Inc. January 17, 2023. Accessed January 18, 2023. https://prn.to/3XEbGK5

Safety, tolerability, pharmacokinetics, and preliminary efficacy, phase 1 study of CMG901. ClinicalTrials.gov. Updated December 28, 2022. Accessed January 18, 2023. https://clinicaltrials.gov/ct2/show/NCT04805307