Overview

This is a multi-center, open-label, dose escalation and dose expansion, Phase 1 study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of CMG901.

The dose escalation part (Part A) will determine the MTD of CMG901 in subjects with relapsed and/or refractory advanced solid tumor for which there is no available standard therapy likely to confer clinical benefit, or the subject is not a candidate for such available therapy based on a modified 3+3 dose escalation design (an accelerated dose titration design followed by traditional 3+3 dose escalation design).

The dose expansion part (Part B) will evaluate the preliminary anti-tumor activity and safety of CMG901 in subjects with Claudin 18.2 positive gastric cancer (GC), gastroesophageal junction (GEJ) cancer, and pancreatic cancer who have relapsed and/or are refractory to approved therapies.

Eligibility

Key Inclusion Criteria:

• Part A: Patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard treatment do not exist, are no longer effective, or are not acceptable to the patient.
• Part A: Must provide archival tumor tissue specimen or agree to undergo a fresh biopsy if archival specimen is unavailable for retrospective Claudin 18.2 testing prior to enrollment; Claudin 18.2 expression is not required for enrollment.
• Part A: Measurable or evaluable disease per RECIST v 1.1.
• Part B: Histologically-confirmed, advanced unresectable or metastatic GC, GEJ adenocarcinoma, or pancreatic cancer which have relapsed and/or are refractory to approved therapies.
• Part B: CLDN18.2-positive tumor sample assessed by central testing. New biopsies and archival bio-samples are allowed. If archival tissue samples from several points of time are available, the most recent one is preferred.
• Part B: Measurable disease per RECIST v 1.1.
• Women of childbearing potential and male subjects must agree to remain abstinent or use contraceptive methods as defined by the protocol.
• Eastern Cooperative Oncology Group Performance Status 0-1.
• Side effects of any prior therapy or procedures for any medical condition has recovered to NCI-CTCAE v.5.0 Grade ≤ 1 or stable status by investigator.

Key Exclusion Criteria:

• Received: chemotherapy or any investigational anti-tumor agents within 28 days of the start of CMG901 treatment; molecularly-targeted agents, immunoconjugate, or antibody drug conjugate within 28 days or or 5 half-lives (whichever is shorter) of the start of CMG901 treatment; major surgery within 28 days of the start of CMG901 treatment; radiotherapy within 21 days of the start of CMG901 treatment; potent cytochrome P450 3A4 (CYP3A4) inhibitors within 14 days or or 5 half-lives (whichever is longer) of the start of CMG901 treatment.
• Diagnosis of immunodeficiency or requiring another form of chronic immunosuppressive therapy. Or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or equivalent) within 7 days prior to the first dose.
• History of severe hypersensitivity to any component or excipient of CMG901.
• Ongoing or active infection assessed by investigator.
• Any severe cardiac dysfunction including left ventricular ejection fraction <50%, congestive heart failure ≥Grade 2 (New York Heart Association), QTc >480 msec, history of acute myocardial infarction, angina pectoris, uncontrolled arrhythmia, acute coronary syndromes, stent placement, stroke, or transient ischemic attack within 6 months of enrollment.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Subjects with uncontrolled ascites, pleural effusion, or pericardial effusion by investigator.
• Preexisting sensory and/or motor neuropathy Grade ≥2.
• Uncontrolled diabetes mellitus or diabetic neuropathy within 3 months of the first dose of CMG901.
• Known infection with HIV, or HIV positive; Known active hepatitis B, or HBsAg positive with HBV-DNA positive, or anti-HBc positive with HBV-DNA positive; Known active hepatitis C, or anti-HCV antibody positive with HCV-RNA positive.
• Any severe and/or uncontrolled systemic disease or other conditions that in the opinion of the Investigator make the subject unsuitable for participation in this study.