Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy, Phase 1 Study of CMG901
- Conditions
- Advanced Solid TumorGastric Cancer(Including Gastroesophageal Junction Adenocarcinoma)Pancreatic Cancer
- Interventions
- Registration Number
- NCT04805307
- Lead Sponsor
- Keymed Biosciences Co.Ltd
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 176
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A, Dose escalation CMG901 CMG901 will be administered in treatment cycles once every 3 weeks (Q3W). Dose escalation will be carried out according to a modified 3+3 dose-escalation design. Accelerated dose titration design will be used for the first 2 dose levels (0.3mg/kg and 0.6mg/kg), and then traditional 3+3 dose escalation design will be used for the following levels (1.2mg/kg, 1.8mg/kg, 2.2mg/kg, 2.6mg/kg and 3.0mg/kg). Part B, Dose expansion,2.2mg/kg CMG901 This cohort will comprise subjects with Claudin 18.2 positive gastric cancer (including gastroesophageal junction adenocarcinoma), pancreatic cancer, and other solid cancer with prior failure of, progression on, or intolerance to, standard therapy. art B, Dose expansion,3.0mg/kg CMG901 This cohort will comprise subjects with Claudin 18.2 positive gastric cancer (including gastroesophageal junction adenocarcinoma), pancreatic cancer, and other solid cancer with prior failure of, progression on, or intolerance to, standard therapy. Part B, Dose expansion,3.0mg/kg CMG901 This cohort will comprise subjects with Claudin 18.2 positive gastric cancer (including gastroesophageal junction adenocarcinoma), pancreatic cancer, and other solid cancer with prior failure of, progression on, or intolerance to, standard therapy.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Part A & Part B: Disease Control Rate (DCR) per RECIST v1.1 up to 24 months Part A & Part B: Overall Survival (OS) up to 24 months Part A: Objective Response Rate (ORR) per RECIST v1.1 up to 24 months Part A & Part B: Area Under the Curve over a dosing interval [AUC(0-tau)] up to 24 months Part A & Part B: Minimum concentration (Cmin) up to 24 months Part A & Part B: Accumulation ratios of peak plasma concentration (Cmax) for multiple doses up to 24 months Part A & Part B: Area Under the Curve from 0 to the time of the last measurable concentration [AUC(0-last)] up to 24 months 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: Duration of Response (DoR) per RECIST v1.1 up to 24 months Part A & Part B: Peak Plasma Concentration (Cmax) up to 24 months Part A & Part B: Terminal elimination half-life (t1/2) up to 24 months Part A & Part B: Volume of distribution (Vz) up to 24 months Part A & Part B: Observed concentration at the end of a dosing interval(Ctrough) 21 days after the first dose Time of maximum observed concentration (Tmax) 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 & Part B: Time of Maximum Observed Concentration (Tmax) 21 days after the first dose Part A & Part B: Volume of distribution at steady-state (Vss) up to 24 months Part A & Part B: Observed concentration at the end of a dosing interval (Ctrough) up to 24 months Part A & Part B: Clearance (CL) up to 24 months 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: Progression Free Survival (PFS) per RECIST v1.1 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
Trial Locations
- Locations (32)
The Second Hospital of Anhui Medical University
🇨🇳Hefei, China
Sun Yat-sen University Cancer Center (SYSUCC)
🇨🇳Guangzhou, Guangdong, China
Affiliated Hospital of Hebei University
🇨🇳Baoding, China
Hunan Cancer Hospital
🇨🇳Changsha, China
Hainan General Hospital
🇨🇳Haikou, China
Jiangxi Cancer Hospital
🇨🇳Nanchang, China
Huashan Hospital, Fudan University
🇨🇳Shanghai, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Sichuan Cancer Hospital
🇨🇳Chengdu, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, China
Fujian Cancer Hosppital
🇨🇳Fuzhou, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
🇨🇳Guangzhou, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, China
The First Affiliated Hospital of Henan University of science and Technology
🇨🇳Luoyang, China
Meizhou People's Hospital
🇨🇳Meizhou, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, China
The First Hospital of China Medical University
🇨🇳Shenyang, China
The Forth Hospital of Hebei Medical University and Hebei Tumor Hospital
🇨🇳Shijiazhuang, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Tongji Hospital Tongji Medical College of HUST
🇨🇳Wuhan, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China