A Study of CM350 in Patients With Advanced Solid Tumors

Official title

A Multicenter, Open Label, Phase I/II Clinical Study of CM350 in Patients With Advanced Solid Tumors

Overview

This is an open label, dose escalation and expansion Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of CM350 in patients with advanced solid tumors. The phase I study consists of a dose escalation phase and a dose expansion phase The safety and tolerability of CM350 and the maximum tolerated dose (MTD) (if applicable) will be evaluated in dose escalation phase. The recommended phase 2 dose (RP2D) of CM350 will be determined in dose expansion phase. The phase II study is to evaluate the efficacy of CM350 at the recommended phase 2 dose (RP2D) for advanced glypican-3 (GPC3)-positive solid tumors.

Interventions

• Biological CM350 group1
  CM350 will be administered intravenously (IV) once a week (QW) through step-up dosing until the participant discontinues study treatment, develops disease progression, initiates a new anti-tumor therapy, develops unacceptable toxicity, death, lost to follow-up, the investigator discontinue study treatment, or a female participant becomes pregnant (whichever occurs first).
• Biological CM350 group2
  CM350 will be administered intravenously (IV) once a week (QW) through step-up dosing until the participant discontinues study treatment, develops disease progression, initiates a new anti-tumor therapy, develops unacceptable toxicity, death, lost to follow-up, the investigator discontinue study treatment, or a female participant becomes pregnant (whichever occurs first).
• Biological CM350 group3
  CM350 will be administered intravenously (IV) once a week (QW). Individual subjects may continue study treatment until the participant discontinues study treatment, develops disease progression, initiates a new anti-tumor therapy, develops unacceptable toxicity, death, lost to follow-up, the investigator discontinue study treatment, or a female participant becomes pregnant (whichever occurs first).

Primary outcome measures

• Dose escalation phase in phase I:Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. [Time frame: Up to 5 years]
• Dose escalation phase in phase I:Dose-Limiting Toxicity (DLT). [Time frame: Up to 7 days after the first target dose]
• Dose escalation phase in phase I:Maximum tolerated dose (MTD) (if applicable). [Time frame: Up to the end of dose escalation phase (3 years)]
• Dose expansion phase in phase I:To determine the recommended Phase 2 Dose (RP2D). [Time frame: Up to 5 years]
• Phase II:To evaluate the efficacy of CM350 in advanced glypican-3-positive solid tumors. [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Phase I & Phase II: Area Under the Curve from 0 to the time of the last quantifiable concentration (AUC0-t). [Time frame: Up to 5 years]
• Phase I & Phase II: To assess the incidence of anti-drug antibody (ADA). [Time frame: Up to 5 years]
• Phase I: To evaluate the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for liver cancer and RECIST v1.1]. [Time frame: Up to 5 years]
• Phase I & Phase II: To evaluate the duration of response (DOR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1). [Time frame: Up to 5 years]
• Phase I & Phase II: To evaluate the disease control rate (DCR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1). [Time frame: Up to 5 years]
• Phase I & Phase II:To evaluate the time to response (TTR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1. [Time frame: Up to 5 years]
• Phase I & Phase II:To evaluate the time to progression (TTP) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1). [Time frame: Up to 5 years]
• Phase I & Phase II:To evaluate the progression-free survival (PFS) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1). [Time frame: Up to 5 years]
• Phase I & Phase II:To evaluate the overall survival (OS) [Time frame: Up to 5 years]
• Phase I & Phase II:To assess the cytokine interleukin-2 (IL-2). [Time frame: Up to 5 years]
• Phase II:Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. [Time frame: Up to 5 years]
• Phase I & Phase II:Area Under the Curve over a dosing interval (AUC tau). [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Patient with histologically or cytologically confirmed advanced solid tumors that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
• hepatocellular-cancer(HCC) participants must have a Barcelona Clinic Liver Cancer (BCLC) stage of B (ineligible for liver surgery and/or other locoregional treatments, or disease progression after locoregional therapy) or stage C , or a China National Liver Cancer (CNLC) stage of IIb or III (ineligible for liver surgery and/or other locoregional treatments, or disease progression after locoregional therapy).
• HCC participants must have a Child-Pugh score of ≤7.
• Phase I dose escalation phase: participants must have evaluable lesions based on RECIST version 1.1.Phase I dose expansion phase and phase II: participants must have at least one measurable lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria

• Patients who have received any cytotoxic chemotherapy, radiotherapy, biological therapy (oncologic vaccines, cytokines, or growth factors for cancer control), or any other investigational anticancer drug treatment (defined as treatments without regulatory approval for any indication) within 28 days before the first dose of CM350.

Note: For palliative radiotherapy to non-central nervous system lesions (total radiotherapy duration ≤14 days) to improve symptoms, a minimum washout period of 7 days before the first dose is required.

• Patients who have received any immunotherapy (including but not limited to PD-1, PD-L1, anti-cytotoxic T-lymphocyte-associated antigen 4 \[CTLA-4\], chimeric antigen receptor T-cell \[CAR-T\] therapy, etc.) within 28 days or 5 half-lives (whichever is shorter) before the first dose of CM350.
• Patients who have received targeted therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of CM350.
• Patients who have previously received any therapy targeting GPC3, including but not limited to monoclonal antibodies, peptide vaccines, CAR-T, and bispecific antibodies.
• Received chronic systemic corticosteroid therapy (daily intake of more than 10 mg prednisone or equivalent doses of other corticosteroids) or any other form of immunosuppressive treatment within 7 days before the first dose of CM350.
• Known active central nervous system metastases. Note: Participants with previously treated brain metastases that have been stable for at least 14 days before the first dose (confirmed by repeat imaging at least 4 weeks apart, with the repeat imaging conducted during the screening period) may be considered for enrollment.
• Participants with uncontrolled pleural effusion, ascites, or pericardial effusion as assessed by the investigator.
• History of other malignancies within 5 years before the first dose of CM350, excluding cured basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast.
• Presence of active infection at screening as assessed by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• West China Hospital of Sichuan University — Chengdu
• Zhongshan Hospital Affiliated to Fudan University — Shanghai

Publications

• Zhou X, Liu Y, Liu X, Song X, Li S, Chen P, Jiang X, Li Y. Novel GPC3 N-terminal bispecific antibody exhibits dual anti-tumor effect against tumor cells. Invest New Drugs. 2025 Jun;43(3):588-601. doi: 10.1007/s10637-025-01530-x. Epub 2025 May 1. PMID 40307410

Identifiers

NCT: NCT05263960 · CM350-030001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗