Advanced Solid Tumor, Gastric Cancer(Including Gastroesophageal Junction Adenocarcinoma), Pancreatic Cancer
Conditions
Brief summary
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 phase (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 phase (Part B) will be conducted in subjects with advanced solid cancer with failure of standard treatment or no standard treatment who are Claudin 18.2 positive to preliminarily explore the efficacy and to determine the RP2D of CMG901.
Interventions
DRUGCMG901
CMG901 will be administered intravenously (IV) on Day 1 of every 21-day cycle. Individual subjects may continue study treatment until confirmed Progressive Disease(PD), unacceptable toxicity, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first.
Sponsors
Keymed Biosciences Co.Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A：Dose Escalation: Modified 3+3 dose escalation design: an accelerated dose titration design followed by traditional 3+3 dose escalation design. Part B：Dose Expansion: Subjects will be enrolled at 2.2 mg/kg, 2.6 mg/kg, 3.0 mg/kg and/or other higher dose levels.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subjects with histologically or cytologically confirmed advanced solid tumors, who have failed to respond to standard of care (progression after treatment or intolerance) or who have no available standard of care regimen. * 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;Subjects enrolled in Part A are not required to be positive for Claudin 18.2. * Part A: Measurable or evaluable lesions per RECIST v 1.1.Part B: At least one measurable lesion per RECIST v1.1. * Part B: Subjects shall provide fresh or archival tumor tissue samples before enrollment for assessment of Claudin 18.2 expression level (central laboratory) and should be positive for Claudin 18.2 as determined by the central laboratory. If the subject can provide positive Claudin 18.2 expression results which had been reported by the same central laboratory using the same method, there is no need for another test. * 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 or interstitial pneumonia 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, major cardiovascular and cerebrovascular diseases (e.g., congestive cardiac failure, acute myocardial infarction, unstable angina, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism) within 6 months prior to the first dose of study drug. * 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. * Subjects with active hepatitis B or C, i.e., positive for anti-HCV antibody and positive for HCV RNA, or positive for HBsAg with detectable positive for HBV DNA (i.e., ≥ 2000 IU/mL). * Any other conditions such as medical history, treatment, laboratory abnormalities that may confound the study results, interfere with the subject's compliance, or impair the interests of the subject, as assessed by the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Incidence of adverse events.Abnormal laboratory parameters, vital signs, 12-lead electrocardiogram and physical examination. Occurrence of Dose-limiting toxicity | Up to 30 days post the last dose, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first. DLTs are up to 21 days after the first dose |
| Part A: To determine the maximum tolerated dose (MTD) of CMG901 | Up to 21 days after the first dose |
| Part B: To preliminarily evaluate the Objective Response Rate (ORR) per RECIST v1.1 of CMG901 in subjects with Claudin 18.2-positive advanced solid cancer | Up to 24 months |
| Part B: Recommended phase II dose | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Part A & Part B: Observed concentration at the end of a dosing interval(Ctrough) | 21 days after the first dose |
| Part A & Part B: Terminal elimination half-life (t1/2) | 21 days after the first dose |
| Part A & Part B: Clearance (CL) | 21 days after the first dose |
| Part A & Part B: Area Under the Curve from 0 to the time of the last measurable concentration [AUC(0-last)] | 21 days after the first dose |
| Part A & Part B: Area Under the Curve over a dosing interval [AUC(0-tau)] | 21 days after the first dose |
| Part A & Part B: Area Under the Curve from 0 to infinity [AUC(0-inf)] | 21 days after the first dose |
| Part A & Part B: Peak Plasma Concentration (Cmax) | 21 days after the first dose |
| Part A & Part B: Time of Maximum Observed Concentration (Tmax) | 21 days after the first dose |
| Part A & Part B: Observed concentration at the end of a dosing interval (Ctrough) | up to 24 months |
| Part A & Part B: Volume of distribution (Vz) | 21 days after the first dose |
| Part A & Part B: Accumulation ratios of area under the curve over a dosing interval [AUC(0-tau)] for multiple doses | up to 24 months |
| Part A & Part B: Incidence of anti-CMG901 | up to 24 months |
| Part A & Part B: Disease Control Rate (DCR) per RECIST v1.1 | up to 24 months |
| Part A & Part B: Duration of Response (DoR) per RECIST v1.1 | up to 24 months |
| Part A & Part B: Progression Free Survival (PFS) per RECIST v1.1 | up to 24 months |
| Part A&B:To evaluate the correlation between clinical efficacy of CMG901 and Claudin 18.2 expression | up to 24 months |
| Part A: Objective Response Rate (ORR) per RECIST v1.1 | up to 24 months |
| Part A & Part B: Overall Survival (OS) | up to 24 months |
| Part B: Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Abnormal laboratory parameters, vital signs, 12-lead electrocardiogram and physical examination | Up to 30 days post the last dose, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first |
| Part A & Part B: Accumulation ratios of peak plasma concentration (Cmax) for multiple doses | up to 24 months |
| Time of maximum observed concentration (Tmax) | up to 24 months |
| Part A & Part B: Volume of distribution at steady-state (Vss) | up to 24 months |
| Part A & Part B: Minimum concentration (Cmin) | up to 24 months |
Countries
China
Outcome results
None listed