A Study of CM350 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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 part (Part A) and a dose extension part (Part B). The safety and tolerability of CM350 and the maximum tolerated dose (MTD) will be evaluated in Part A. The safety, tolerability and efficacy of CM350 at MTD and/or the dose of one level less than MTD (MTD-1), and the recommended dose level for the phase II study will be determined in Part B.

Official Title
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A Multicenter, Open Label, Single-arm, Phase I/II Clinical Study of CM350 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: CM350_group 1
* Drug: CM350_group 2
* Drug: CM350_group 3
* Drug: CM350_group 4
* Drug: CM350_group 5a
* Drug: CM350_group 5b
* Drug: CM350_group 6a
* Drug: CM350_group 6b
* Drug: CM350_group 7
* Drug: CM350_group 8
* Drug: CM350_MTD level
* Drug: CM350_MTD-1 level


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dose escalation part of Phase I study : Patient with histologically or cytologically confirmed advanced solid tumors for which standard treatment do not exist, are no longer effective, or are not acceptable to the patient. Dose expansion part of Phase I study : Patient with histologically or cytologically confirmed IHC GPC3-positive advanced solid tumors for which standard treatment do not exist, are no longer effective, or are not acceptable to the patient. Exclusion Criteria: Patients who received any cytotoxic chemotherapy agent, radiotherapy, targeted therapy, biotherapy, antitumor traditional Chinese medicine, or any other investigational antitumor agent within 28 days prior to first dosing of CM350. Had major surgery within 28 days prior to first dosing of CM350. Received any antibodies/drugs/therapies targeting T-cell co-regulatory proteins (immune checkpoints) within 28 days or 5 half-lives (whichever is shorter) prior to first dosing of CM350, including but not limited to cytokine therapy, anti-programmed death receptor 1 (PD-1), anti-programmed death receptor ligand-1 (PD-L1), anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), chimeric antigen receptor T cell (CAR T) therapy, etc. Received therapies targeting GPC3, including but not limited to monoclonal antibodies, peptide vaccines, chimeric antigen receptor T cells (CAR-T), and bispecific antibodies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Dose escalation<br>There are 10 dose groups in dose escalation part. | Drug: CM350_group 1<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 5ug of CM350 on the first day of first cycle (C1D1), 5ug on C1D8, 5ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 2<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 15ug of CM350 on the first day of first cycle (C1D1), 15ug on C1D8, 15ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 3<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 45ug of CM350 on the first day of first cycle (C1D1), 45ug on C1D8, 45ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 4<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 45ug of CM350 on the first day of first cycle (C1D1), 135ug on C1D8, 135ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 5a<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 45ug of CM350 on the first day of first cycle (C1D1), 135ug on C1D8, 270ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 5b<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 135ug of CM350 on the first day of first cycle (C1D1), 135ug on C1D8, 135ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 6a<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 45ug of CM350 on the first day of first cycle (C1D1), 135ug on C1D8, 405ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 6b<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 135ug of CM350 on the first day of first cycle (C1D1), 270ug on C1D8, 270ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 7<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 135ug of CM350 on the first day of first cycle (C1D1), 405ug on C1D8, 405ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM350_group 8<br>* CM350 will be administered intravenously (IV) once a week (QW). Patients will take 405ug of CM350 on the first day of first cycle (C1D1), 405ug on C1D8, 405ug on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>|
| Experimental: Part B, Dose expansion<br>Based on the data of part A, one (MTD or the dose of one level less than MTD) or two (MTD and the dose of one level less than MTD) dose levels will be discussed for further evaluation in part B. | Drug: CM350_MTD level<br>* CM350 will be administered intravenously (IV) once a week (QW). 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.<br>Drug: CM350_MTD-1 level<br>* CM350 will be administered intravenously (IV) once a week (QW). 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation part and dose expansion part : Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Up to 3 years | 
| Dose escalation part: Dose-Limiting Toxicity (DLT) | Dose-Limiting Toxicity (DLT) | Up to 21 days after the first dose | 
| Dose escalation part: maximum tolerated dose (MTD) | Maximum tolerated dose (MTD) | Up to the end of dose escalation part (1 year) | 
| Dose expansion part: recommended phase II dose (RP2D) | Recommended phase II dose (RP2D) | Up to the end of dose expansion part (2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with positive anti-drug antibody (ADA) and neutralizing antibody (Nab) | Proportion of subjects with positive anti-drug antibody (ADA) and neutralizing antibody (Nab) | Up to 3 years | 
| Overall Survival (OS) | Overall Survival (OS) | Up to 3 years | 
| Overall Response Rate (ORR), assessed according to RECIST v1.1 | Overall Response Rate (ORR), assessed according to RECIST v1.1 | Up to 3 years | 
| Duration of Response (DOR), assessed according to RECIST v1.1 | Duration of Response (DOR), assessed according to RECIST v1.1 | Up to 3 years | 
| Disease Control Rate (DCR), assessed according to RECIST v1.1 | Disease Control Rate (DCR), assessed according to RECIST v1.1 | Up to 3 years | 
| Progression Free Survival (PFS), assessed according to RECIST v1.1 | Progression Free Survival (PFS), assessed according to RECIST v1.1 | Up to 3 years | 
| Time to progression (TTP), assessed according to RECIST v1.1 | Time to progression (TTP), assessed according to RECIST v1.1 | Up to 3 years |