Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy, Phase 1 Study of CMG901

NCT ID: NCT04805307

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-24
• Study Completion Date: 2024-04-05

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.

Conditions

Advanced Solid Tumor; Gastric Cancer(Including Gastroesophageal Junction Adenocarcinoma); Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A, Dose escalation

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).

Group Type: EXPERIMENTAL

CMG901

Intervention Type: DRUG

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.

Part B, Dose expansion,2.2mg/kg

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.

Group Type: EXPERIMENTAL

CMG901

Intervention Type: DRUG

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.

art B, Dose expansion,3.0mg/kg

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.

Group Type: EXPERIMENTAL

CMG901

Intervention Type: DRUG

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.

Part B, Dose expansion,3.0mg/kg

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.

Group Type: EXPERIMENTAL

CMG901

Intervention Type: DRUG

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.

Interventions

CMG901

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.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Keymed Biosciences Co.Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ruihua Xu

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center (SYSUCC)

Guangzhou, Guangdong, China

Henan Cancer Hospital

Zhengzhou, Henan, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Affiliated Hospital of Hebei University

Baoding, , China

Hunan Cancer Hospital

Changsha, , China

Sichuan Cancer Hospital

Chengdu, , China

Chongqing University Cancer Hospital

Chongqing, , China

Fujian Cancer Hosppital

Fuzhou, , China

Fujian Medical University Union Hospital

Fuzhou, , China

The First Affiliated Hospital of Fujian Medical University

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

Hainan General Hospital

Haikou, , China

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, , China

Harbin Medical University Cancer Hospital

Harbin, , China

The Second Hospital of Anhui Medical University

Hefei, , China

Affiliated Hospital of Jining Medical University

Jining, , 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

Jiangxi Cancer Hospital

Nanchang, , China

Huashan Hospital, Fudan University

Shanghai, , 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

Countries

China

References

Ruan DY, Liu FR, Wei XL, Luo SX, Zhuang ZX, Wang ZN, Liu FN, Zhang YQ, Yang JW, Chen ZD, Wang YS, Wang JY, Liang XH, Wu XJ, Zheng YL, Liu J, Shi X, Kumar R, Liu W, Chen B, Zhang DS, Xu RH. Claudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial. Lancet Oncol. 2025 Feb;26(2):227-238. doi: 10.1016/S1470-2045(24)00636-3. Epub 2025 Jan 6.

Reference Type: DERIVED

PMID: 39788133 (View on PubMed)

Other Identifiers

KYM901

Identifier Type: -

Identifier Source: org_study_id