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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04805307
• Other study ID #: KYM901
• Status: Recruiting
• Phase: Phase 1
• Start date: December 24, 2020
• Est. completion date: October 2024

Study information

• Verified date: December 2022
• Source: Keymed Biosciences Co.Ltd
• Contact: Qian Jia
• Phone: 028-88610620
• Email: qianjia[@]keymedbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 part (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 part (Part B) will evaluate the preliminary anti-tumor activity and safety of CMG901 in subjects with Claudin 18.2 positive gastric cancer (GC), gastroesophageal junction (GEJ) cancer, and pancreatic cancer who have relapsed and/or are refractory to approved therapies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: October 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Part A: Patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard treatment do not exist, are no longer effective, or are not acceptable to the patient.
• 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; Claudin 18.2 expression is not required for enrollment.
• Part A: Measurable or evaluable disease per RECIST v 1.1.
• Part B: Histologically-confirmed, advanced unresectable or metastatic GC, GEJ adenocarcinoma, or pancreatic cancer which have relapsed and/or are refractory to approved therapies.
• Part B: CLDN18.2-positive tumor sample assessed by central testing. New biopsies and archival bio-samples are allowed. If archival tissue samples from several points of time are available, the most recent one is preferred.
• Part B: Measurable disease per RECIST v 1.1.
• 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 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, history of acute myocardial infarction, angina pectoris, uncontrolled arrhythmia, acute coronary syndromes, stent placement, stroke, or transient ischemic attack within 6 months of enrollment.
• 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.
• Known infection with HIV, or HIV positive; Known active hepatitis B, or HBsAg positive with HBV-DNA positive, or anti-HBc positive with HBV-DNA positive; Known active hepatitis C, or anti-HCV antibody positive with HCV-RNA positive.
• Any severe and/or uncontrolled systemic disease or other conditions that in the opinion of the Investigator make the subject unsuitable for participation in this study.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Pancreatic Cancer

Intervention

Drug:
• CMG901
CMG901 will be administered intravenously (IV) on Day 1 of every 21-day cycle. Individual subjects may continue study treatment until there is evidence of disease progression (clinical or radiologic) judged by Investigators, unacceptable toxicity or other reasons for treatment discontinuation.

Locations

Country	Name	City	State
China	Affiliated Hospital of Hebei University	Baoding
China	Hunan Cancer Hospital	Changsha
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital of Sichuan University	Chengdu	Sichuan
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	Sun Yat-sen University Cancer Center (SYSUCC)	Guangzhou	Guangdong
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	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Keymed Biosciences Co.Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of Participants with a Dose-Limiting Toxicity (DLT)		Up to 21 days after the first dose
Primary	Part A: Incidence, severity, and outcome of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0		Up to 30 days after the last dose of CMG901 or until the start of subsequent anticancer therapy, if earlier
Primary	Part B: Objective Response Rate, Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)		Up to 24 months
Primary	Part B: Recommended phase II dose		Up to 24 months
Secondary	Part A & Part B: AUC to the last quantifiable concentration [AUC(0-last)], over the dosing interval [AUC(0-tau)], extrapolated to infinity [AUC(0-inf), time to Cmax (tmax), apparent half-life (t1/2), systemic clearance (CL).		21 days after the first dose
Secondary	Part A & Part B: AUC(0-last), AUC(0-tau), Cmax, tmax, t1/2, systemic clearance (CL), volume of distribution (Vz, Vss), minimum concentration (Cmin), Ctrough, accumulation ratios for Cmax and AUC(0-tau) for multiple doses		up to 24 months
Secondary	Part A & Part B: Incidence of anti-CMG901		up to 24 months
Secondary	Part A & Part B: Disease Control Rate, Assessed According to RECIST v1.1		up to 24 months
Secondary	Part A & Part B: Duration of Response, Assessed According to RECIST v1.1		up to 24 months
Secondary	Part A & Part B: Progression Free Survival, Assessed According to RECIST v1.1		up to 24 months
Secondary	Part A: Claudin 18.2 expression by retrospective testing in tumor specimens by immunohistochemistry		up to 24 months
Secondary	Part A: ORR, Assessed according to RECIST 1.1		Up to 24 months
Secondary	Part A & Part B: Overall Survival		Up to 24 months
Secondary	Part B: Incidence, severity, and outcome of TEAEs and SAEs based on NCI CTCAE version 5.0		Up to 24 months