A Phase Ib/II Study Of JS015 Combination Therapy in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase Ib/II, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of JS015 combination therapy in patients with advanced solid tumors. The Recommended dose for phase II trial （RP2D） will be determined based on the safety, tolerability, pharmacokinetics and efficacy.

Official Title
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A Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of JS015 Combination Therapy in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Biological: JS015
* Biological: Toripalimab
* Biological: Paclitaxel
* Drug: Irinotecan
* Drug: Capecitabine
* Drug: Oxaliplatin
* Biological: Bevacizumab
* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Gemcitabine
* Drug: Albumin-Bound Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients who meet the following criteria for each indication cohort: Esophageal cancer cohort, patients with histologically or cytologically confirmed esophageal squamous cell carcinoma with locally advanced unresectable or with distant metastasis, who progressed during or after prior first-line PD-(L)1 antibody and platinum-based chemotherapy; Gastric cancer cohort, patients with histologically or cytologically confirmed gastric/gastroesophageal junction adenocarcinoma with locally advanced unresectable or distant metastases, HER2-negative, who progressed during or after prior first-line PD-(L)1 antibody and platinum-based chemotherapy; 1L gastric cancer cohort, patients with histologically or cytologically confirmed gastric/gastroesophageal junction adenocarcinoma with HER2-negative results and no prior systemic antitumor therapy; Colorectal cancer cohort, patients with histologically confirmed adenocarcinoma of the colon or rectum, who progressed during or after first-line 5-FU-based combination therapy; Pancreatic cancer cohort, patients with histologically or cytologically confirmed locally advanced unresectable or distant metastatic pancreatic ductal adenocarcinoma, who have not received any previous systemic antitumor therapy 2 . Eastern Cooperative Oncology Group (ECOG) 0 or 1; 3. Life expectancy >=12 weeks; 4. At least one measurable lesion according to RECIST 1.1; 5. Adequate organ function; Exclusion Criteria: Leptomeningeal metastases and /or active brain metastases; Pleural, peritoneal, or pericardial effusion with clinical symptoms or requiring repeated management (puncture, drainage, etc.); History of interstitial lung disease or a previous history of noninfectious pneumonia with corticosteroid therapy, or evidence of active pneumonia on screening imaging; History of immunodeficiency; History of serious cardiovascular and/or cerebrovascular diseases; History of abdominal or tracheo-esophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months before the first dose of administration

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: esophogeal squamous carcinoma<br>In Cohort 1, patients will be treated with JS015 in combination with paclitaxel or irinotecan | Biological: JS015<br>* JS015 will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or day 1 every 21 day cycle, based on different combined chemotherapy.<br>Biological: Paclitaxel<br>* Paclitaxel will be administered intravenously (IV) on day 1 every 21 day cycle.<br>Drug: Irinotecan<br>* Irinotecan will be administered intravenously (IV) on days 1 and 15 every 28 day cycle.<br>|
| Experimental: Cohort 2: gastric cancer<br>In Cohort 2, patients will be treated with JS015 in combination with paclitaxel | Biological: JS015<br>* JS015 will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or day 1 every 21 day cycle, based on different combined chemotherapy.<br>Biological: Paclitaxel<br>* Paclitaxel will be administered intravenously (IV) on day 1 every 21 day cycle.<br>|
| Experimental: Cohort 3: gastric cancer<br>In Cohort 3, patients will be treated with JS015 in combination with toripalimab and XELOX | Biological: JS015<br>* JS015 will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or day 1 every 21 day cycle, based on different combined chemotherapy.<br>Biological: Toripalimab<br>* Toripalimab will be administered intravenously (IV) on day 1 every 21 day cycle.<br>Drug: Capecitabine<br>* Capecitabin will be administered orally twice daily from day 1 to 14 every 21 day cycle.<br>Drug: Oxaliplatin<br>* Oxaliplatin will be administered intravenously (IV) on day 1 every 21 day cycle.<br>|
| Experimental: Cohort 4: colorectal cancer<br>In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI | Biological: JS015<br>* JS015 will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or day 1 every 21 day cycle, based on different combined chemotherapy.<br>Drug: Irinotecan<br>* Irinotecan will be administered intravenously (IV) on days 1 and 15 every 28 day cycle.<br>Drug: Capecitabine<br>* Capecitabin will be administered orally twice daily from day 1 to 14 every 21 day cycle.<br>Drug: Oxaliplatin<br>* Oxaliplatin will be administered intravenously (IV) on day 1 every 21 day cycle.<br>Biological: Bevacizumab<br>* Bevacizumab will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or day 1 every 21 day cycle, based on different combined chemotherapy.<br>Drug: Fluorouracil<br>* Fluorouracil will be administered intravenously (IV) on days 1 and 15 every 28 day cycle.<br>Drug: Leucovorin<br>* Leucovorin will be administered intravenously (IV) on days 1 and 15 every 28 day cycle.<br>|
| Experimental: Cohort 5: pancreatic cancer<br>In Cohort 5, patients will be treated with JS015 in combination with toripalimab, albumin-bound paclitaxel and gemcitabine | Biological: JS015<br>* JS015 will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or day 1 every 21 day cycle, based on different combined chemotherapy.<br>Biological: Toripalimab<br>* Toripalimab will be administered intravenously (IV) on day 1 every 21 day cycle.<br>Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously (IV) on days 1 and 8 every 21 day cycle.<br>Drug: Albumin-Bound Paclitaxel<br>* Albumin-bound paclitaxel will be administered intravenously (IV) on days 1 and 8 every 21 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of dose-limiting toxicity （DLT） | incidence and severity of DLT | 2 Years | 
| incidence of adverse event（AE） | adverse events (AE) | 2 Years | 
| Recommended dose for phase II trial RP2D | Recommended dose for phase II trial | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak concentration (Cmax) | The highest plasma drug concentration that can be achieved after medication | 2 years | 
| time to peak concentration（Tmax） | The time it takes for the drug to reach its maximum concentration (Cmax) in the plasma after administration | 2 years | 
| elimination half life（t1/2） | The time it takes for the concentration of the drug in the plasma to be reduced by 50% | 2 years | 
| immunogenicity | Incidence of Anti-Drug Antibody (ADA) | 2 years | 
| Objective response rate (ORR) based on Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1) | Defined as the proportion of subjects who achieved partial response (PR) or complete response (CR) | 2 years | 
| Progression free survival (PFS) | The time from first dose to Disease progression or death | 2 years | 
| overall survival (OS) | The time from first dose to death from any cause | 2 years |