Clinical trial NCT04805307: Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy, Phase 1 Study of CMG901
Official title: An Open-Label, Phase 1, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of CMG901 in Subjects With Advanced Unresectable or Metastatic Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Gastric Cancer(Including Gastroesophageal Junction Adenocarcinoma)
Pancreatic Cancer
Lead sponsor: Keymed Biosciences Co.Ltd
Sponsor class: INDUSTRY
First posted: 2021-03-18
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Part A: Incidence of adverse events.Abnormal laboratory parameters, vital signs, 12-lead electrocardiogram and physical examination. Occurrence of Dose-limiting toxicity
timeFrame: 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
measure: Part A: To determine the maximum tolerated dose (MTD) of CMG901
timeFrame: Up to 21 days after the first dose
measure: 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
timeFrame: Up to 24 months
measure: Part B: Recommended phase II dose
timeFrame: Up to 24 months
Secondary outcomes:
measure: Part A & Part B: Area Under the Curve from 0 to the time of the last measurable concentration [AUC(0-last)]
timeFrame: 21 days after the first dose
measure: Part A & Part B: Area Under the Curve over a dosing interval [AUC(0-tau)]
timeFrame: 21 days after the first dose
measure: Part A & Part B: Area Under the Curve from 0 to infinity [AUC(0-inf)]
timeFrame: 21 days after the first dose
measure: Part A & Part B: Peak Plasma Concentration (Cmax)
timeFrame: 21 days after the first dose
measure: Part A & Part B: Time of Maximum Observed Concentration (Tmax)
timeFrame: 21 days after the first dose
measure: Part A & Part B: Terminal elimination half-life (t1/2)
timeFrame: 21 days after the first dose
measure: Part A & Part B: Clearance (CL)
timeFrame: 21 days after the first dose
measure: Part A & Part B: Volume of distribution (Vz)
timeFrame: 21 days after the first dose
measure: Part A & Part B: Observed concentration at the end of a dosing interval(Ctrough)
timeFrame: 21 days after the first dose
measure: Part A & Part B: Area Under the Curve from 0 to the time of the last measurable concentration [AUC(0-last)]
timeFrame: up to 24 months
measure: Part A & Part B: Area Under the Curve over a dosing interval [AUC(0-tau)]
timeFrame: up to 24 months
measure: Part A & Part B: Peak Plasma Concentration (Cmax)
timeFrame: up to 24 months
measure: Time of maximum observed concentration (Tmax)
timeFrame: up to 24 months
measure: Part A & Part B: Terminal elimination half-life (t1/2)
timeFrame: up to 24 months
measure: Part A & Part B: Clearance (CL)
timeFrame: up to 24 months
measure: Part A & Part B: Volume of distribution (Vz)
timeFrame: up to 24 months
measure: Part A & Part B: Volume of distribution at steady-state (Vss)
timeFrame: up to 24 months
measure: Part A & Part B: Minimum concentration (Cmin)
timeFrame: up to 24 months
measure: Part A & Part B: Observed concentration at the end of a dosing interval (Ctrough)
timeFrame: up to 24 months
measure: Part A & Part B: Accumulation ratios of peak plasma concentration (Cmax) for multiple doses
timeFrame: up to 24 months
measure: Part A & Part B: Accumulation ratios of area under the curve over a dosing interval [AUC(0-tau)] for multiple doses
timeFrame: up to 24 months
measure: Part A & Part B: Incidence of anti-CMG901
timeFrame: up to 24 months
measure: Part A & Part B: Disease Control Rate (DCR) per RECIST v1.1
timeFrame: up to 24 months
measure: Part A & Part B: Duration of Response (DoR) per RECIST v1.1
timeFrame: up to 24 months
measure: Part A & Part B: Progression Free Survival (PFS) per RECIST v1.1
timeFrame: up to 24 months
measure: Part A&B:To evaluate the correlation between clinical efficacy of CMG901 and Claudin 18.2 expression
timeFrame: up to 24 months
measure: Part A: Objective Response Rate (ORR) per RECIST v1.1
timeFrame: up to 24 months
measure: Part A & Part B: Overall Survival (OS)
timeFrame: up to 24 months
measure: 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
timeFrame: Up to 30 days post the last dose, initiation of new anti-tumor therapy, withdrawal from the study, or death, whichever occurs first
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center (SYSUCC)
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hosppital
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Haikou
country: China
facility: Hainan General Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and Technology
city: Meizhou
country: China
facility: Meizhou People's Hospital
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Shijiazhuang
country: China
facility: The Forth Hospital of Hebei Medical University and Hebei Tumor Hospital
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu
role: PRINCIPAL_INVESTIGATOR
References: