FDA Grants Fast Track Status to CMG901 for Unresectable/Metastatic Gastric/GEJ Cancer

The FDA has granted fast track designation to single-agent CMG901 for the treatment of patients with unresectable or metastatic gastric and gastroesophageal junction cancer who have relapsed and/or are refractory to approved therapies, according to an announcement by Keymed Biosciences.¹

CMG901 is an Claudin 18.2-targeted agent. It works by binding to Claudin 18.2-positive cells. CMG901 then goes into the lysosome by tumor cells and releases the cytotoxic payload. This process halts the cell cycles as well as the apoptosis of the tumor cells. CMG901 has also been shown to stimulate cellular and soluble immune effectors to limit activation of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, killing Claudin 18.2-positive cells.

In preclinical studies, the Claudin 18.2-targeted agent was effective at destroying gastric cancer cells with higher potency when compared with zolbetuximab analog or the unconjugated antibody of CMG901. The agent was also well-tolerated in the gastric cancer model and demonstrated a favorable safety profile.

Currently, an open-label, phase 1, dose-escalation, and dose-expansion study (NCT04805307) is underway to test the safety, tolerability, and preliminary efficacy of CMG901 in patients with advanced, unresectable, or metastatic solid tumors.^1,2 In 2 parts, the study aims to enroll 162 patients evaluate the primary end points of the number of patients with dose-limiting toxicity and the incidence, severity, and outcome of treatment-emergent adverse events (TEAEs) and serious AEs in the Part A. In Part B, the primary end point will include the objective response rate assessed by RECIST v1.1, and determining the recommended phase 2 dose of CMG901.²

Secondary end points that will be explored in both parts of the study include the area under the curve, the incidence of anti-CMG901, disease control rate, duration of response, progression-free survival, and overall survival. Part A secondary end points include Claudin 18.2 expression and ORR, and the 1 secondary end point explored only in Part B is the incidence, severity, and outcome of TEAEs and SAEs.

To be eligible for Part A, patients are required to have a histologically or cytologically confirmed advanced and/or metastatic solid tumor. Archival tissue to biopsy, measurable disease, and an ECOG performance status. Requirements for Part B are the same, with the exception that patients must have histologically-confirmed, advanced unresectable or metastatic GC, GEJ adenocarcinoma, or pancreatic cancer that is relapsed and/or are refractory to approved therapies.

Participation in the study is not permitted to patients who have previously received chemotherapy or any investigational anti-tumor agents within 28 days of the start of CMG901 treatment. Treatment with molecularly-targeted agents, immunoconjugate, or antibody-drug conjugate within 28 days is also grounds for exclusion, along with major surgery within 28 days, radiotherapy within 21 days, or potent cytochrome P450 3A4 inhibitors within 14 days. Patients with certain comorbidities such as cardiac dysfunction, active central nervous system metastases, uncontrolled diabetes, and more are not eligible to enroll.

CMG90 is the only drug in its class to have received fast-track status to date. Prior to its fast track status, the drug was granted orphan drug designation by the FDA.¹

_REFERENCES:

_{1. FDA granted CMG901 fast track designation for unresectable or metastatic gastric and gastroesophageal junction cancer which have relapsed and/or are refractory to approved therapies. News release. Keymed Biosciences. April 19, 2022. Accessed April 22, 2022.}

_{2. Safety, tolerability, pharmacokinetics, and preliminary efficacy, phase 1 study of CMG901. Clinicaltrials.gov. Update December 9, 2021. Accessed April 22, 2022.}