Safety and Efficacy of IMM01 Plus Tislelizumab in Patients With Advanced Solid Tumors and Lymphomas

Study Overview
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Brief Summary
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This is an open-label, multicenter, phase 1b/2 trial of IMM01 (SIRPα Fc) plus tislelizumab in patients with advanced solid tumors and lymphomas.

Detailed Description
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This open-label, multicenter, phase 1b/2 trial is conducted to evaluate the safety, tolerability and preliminary activity in patients with advanced solid tumors and lymphomas. This trial includes two parts: the phase 1b dose escalation part and the phase 2 dose expansion part. In the dose escalation part with a standard 3+3 design, IMM01 (1.0, 1.5, 2.0 mg/kg) was administered once a week and tislelizumab (200mg) was administered once every 3 weeks. In the dose expansion part, IMM01 (the dose determined in the dose escalation part) was administered once a week and tislelizumab (200mg) was administered once every 3 weeks. And the cohorts includes HNSCC, NSCLC, SCLC, R/R cHL and others.

Official Title
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A Phase 1b/2 Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, and Efficacy of IMM01 Plus Tislelizumab in Patients With Advanced Solid Tumors and Lymphomas

Conditions
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Solid Tumor, Classic Hodgkin Lymphoma

Intervention / Treatment
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* Drug: IMM01
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old, male or female Life expectancy≥12 weeks; Phase 1b: Patients with advanced solid tumors diagnosed by histology or cytology, who have been failure to previous standard treatments; Phase 2: Patients with HNSCC, NPC, OC, NSCLC, SCLC, HCC, cHL and other solid tumors diagnosed by histology or cytology, who have been failure to first-line standard treatment (including PD-1/L1) at least; ECOG PS of 0 or 1; Adequate organs function, including bone marrow, hepatic, renal, cardiac, coagulation. Adverse events associated with previous anti-tumor therapy have returned to≤ grade 1(NCI CTCAE V5.0); Exclusion Criteria: Previous treatment with CD47 inhibitor/SIRPαinhibitor or fusion protein; Patients with symptomatic or progressive central nervous system (CNS) metastasis; Uncontrolled hypertension, pulmonary hypertension or unstable angina, myocardial infarction within 6 months prior to administration; a history of chronic heart failure (NYHA G3/4); severe arrhythmia; A history of arterial thrombosis, deep venous thrombosis and pulmonary embolism within 3 months prior to administration; A history of moderate or severe dyspnea, interstitial lung disease (ILD) or servre pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency; With other malignant tumors; Diseases that may cause gastrointestinal bleeding or perforation; Uncontrollable pleural, peritoneal or pericardial effusions; A history of immunodeficiency; A history of autoimmune diseases; Uncontrolled severe active infections.

Ages Eligible for Study
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Minimum Age: 18 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: Dose Escalation Part<br>Mutiple dose level cohorts in the dose escalation part | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|
| Experimental: Head and neck squamous cell carcinoma, nasopharyngeal carcinoma<br>Dose expansion cohort with IMM01 plus Tislelizumab | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|
| Experimental: Ovarian carcinoma<br>Dose expansion cohort with IMM01 plus Tislelizumab | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|
| Experimental: Non small cell lung carcinoma, small cell lung carcinoma<br>Dose expansion cohort with IMM01 plus Tislelizumab | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|
| Experimental: Hepatocellular carcinoma<br>Dose expansion cohort with IMM01 plus Tislelizumab | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|
| Experimental: Other solid tumors<br>Dose expansion cohort with IMM01 plus Tislelizumab | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|
| Experimental: Classic hodgkin lymphoma<br>Dose expansion cohort with IMM01 plus Tislelizumab | Drug: IMM01<br>* IMM01 (1.0, 1.5, 2.0 mg/kg) QW IV in the dose escalation part. IMM01 (dose determined in the dose escalation part) QW IV in the dose expansion part.<br>* Other names: SIRPα Fc;Drug: Tislelizumab<br>* Tislelizumab 200mg Q3W IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity in dose escalation part |  | DLT observation 21 days | 
| MTD/RP2D in dose escalation part |  | DLT observation 21 days | 
| ORR in dose expansion part |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TRAEs |  | up to 12 months | 
| PFS |  | up to 12 months | 
| DOR |  | up to 12 months | 
| DCR |  | up to 12 months | 
| Cmax |  | up to 12 months | 
| T1/2 |  | up to 12 months | 
| AUC |  | up to 12 months | 
| ADA |  | up to 12 months |