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

NCT04805307 | Completed Phase 1

• 1 other identifier: KYM901
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 32

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (29)

• 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

Study Arms (4)

Part A, Dose escalation

EXPERIMENTAL

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).

Drug: CMG901

Part B, Dose expansion,2.2mg/kg

EXPERIMENTAL

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.

Drug: CMG901

art B, Dose expansion,3.0mg/kg

EXPERIMENTAL

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.

Drug: CMG901

Part B, Dose expansion,3.0mg/kg

EXPERIMENTAL

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.

Drug: CMG901

Interventions

CMG901 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 A, Dose escalation; Part B, Dose expansion,2.2mg/kg; Part B, Dose expansion,3.0mg/kg; art B, Dose expansion,3.0mg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Keymed Biosciences Co.Ltd: lead

Study Sites (32)

Sun Yat-sen University Cancer Center (SYSUCC)

Guangzhou, Guangdong, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Affiliated Hospital of Hebei University

Baoding, China

Location

Hunan Cancer Hospital

Changsha, China

Location

Sichuan Cancer Hospital

Chengdu, China

Location

Chongqing University Cancer Hospital

Chongqing, China

Location

Fujian Cancer Hosppital

Fuzhou, China

Location

Fujian Medical University Union Hospital

Fuzhou, China

Location

The First Affiliated Hospital of Fujian Medical University

Fuzhou, China

Location

Guangdong Provincial People's Hospital

Guangzhou, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, China

Location

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, China

Location

Hainan General Hospital

Haikou, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, China

Location

Harbin Medical University Cancer Hospital

Harbin, China

Location

The Second Hospital of Anhui Medical University

Hefei, China

Location

Affiliated Hospital of Jining Medical University

Jining, China

Location

Lanzhou University Second Hospital

Lanzhou, China

Location

The First Affiliated Hospital of Henan University of science and Technology

Luoyang, China

Location

Meizhou People's Hospital

Meizhou, China

Location

Jiangxi Cancer Hospital

Nanchang, China

Location

Huashan Hospital, Fudan University

Shanghai, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, China

Location

The First Hospital of China Medical University

Shenyang, China

Location

The Forth Hospital of Hebei Medical University and Hebei Tumor Hospital

Shijiazhuang, China

Location

The Second Affiliated Hospital of Soochow University

Suzhou, China

Location

Hubei Cancer Hospital

Wuhan, China

Location

Tongji Hospital Tongji Medical College of HUST

Wuhan, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, China

Location

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

Related Publications (1)

• 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.

  PMID: 39788133 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Ruihua Xu

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 18, 2021
• Study Start: December 24, 2020
• Primary Completion: April 5, 2024
• Study Completion: April 5, 2024
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (32)