Clinical trial NCT05263960: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Keymed Biosciences Co.Ltd
Sponsor class: INDUSTRY
First posted: 2022-03-03
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: 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.
timeFrame: Up to 5 years
measure: Dose escalation phase in phase I:Dose-Limiting Toxicity (DLT).
timeFrame: Up to 7 days after the first target dose
measure: Dose escalation phase in phase I:Maximum tolerated dose (MTD) (if applicable).
timeFrame: Up to the end of dose escalation phase (3 years)
measure: Dose expansion phase in phase I:To determine the recommended Phase 2 Dose (RP2D).
timeFrame: Up to 5 years
measure: Phase II:To evaluate the efficacy of CM350 in advanced glypican-3-positive solid tumors.
timeFrame: Up to 5 years
Secondary outcomes:
measure: Phase I & Phase II: Area Under the Curve from 0 to the time of the last quantifiable concentration (AUC0-t).
timeFrame: Up to 5 years
measure: Phase I & Phase II: To assess the incidence of anti-drug antibody (ADA).
timeFrame: Up to 5 years
measure: 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].
timeFrame: Up to 5 years
measure: Phase I & Phase II: To evaluate the duration of response (DOR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).
timeFrame: Up to 5 years
measure: Phase I & Phase II: To evaluate the disease control rate (DCR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To evaluate the time to response (TTR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1.
timeFrame: Up to 5 years
measure: Phase I & Phase II:To evaluate the time to progression (TTP) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To evaluate the progression-free survival (PFS) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To evaluate the overall survival (OS)
timeFrame: Up to 5 years
measure: Phase I & Phase II:To assess the cytokine interleukin-2 (IL-2).
timeFrame: Up to 5 years
measure: Phase II:Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.
timeFrame: Up to 5 years
measure: Phase I & Phase II:Area Under the Curve over a dosing interval (AUC tau).
timeFrame: Up to 5 years
measure: Phase I & Phase II:Peak Plasma Concentration (Cmax).
timeFrame: Up to 5 years
measure: Phase I & Phase II:Time of Maximum Observed Concentration (Tmax).
timeFrame: Up to 5 years
measure: Phase I & Phase II:Observed concentration at the end of a dosing interval (Ctrough).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To assess the cytokine interleukin-6 (IL-6).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To assess the cytokine interleukin-10 (IL-10).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To assess the cytokine interferon-gamma(IFN-γ).
timeFrame: Up to 5 years
measure: Phase I & Phase II:To assess the cytokine tumor necrosis factor-alpha (TNF-α).
timeFrame: Up to 5 years
measure: Phase I & Phase II: To assess the Immunophenotyping cluster of differentiation 3 positive (CD3+).
timeFrame: Up to 5 years
measure: Phase I & Phase II: To assess the Immunophenotyping cluster of differentiation 4 positive (CD4+).
timeFrame: Up to 5 years
measure: Phase I & Phase II: To assess the Immunophenotyping cluster of differentiation 8 positive (CD8+).
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Jia Fan
role: PRINCIPAL_INVESTIGATOR
References: