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

Sponsor

Shanghai Junshi Bioscience Co., Ltd. (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06139211

Collaborator

Sponsor GmbH (Other)

186

Enrollment

Location

Arms

Anticipated Duration (Months)

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Biological: JS015 Biological: Toripalimab Biological: Paclitaxel Drug: Irinotecan Drug: Capecitabine Drug: Oxaliplatin Biological: Bevacizumab Drug: Fluorouracil Drug: Leucovorin Drug: Gemcitabine Drug: Albumin-Bound Paclitaxel	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

186 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 30, 2023

Anticipated Primary Completion Date :

Nov 30, 2025

Anticipated Study Completion Date :

Apr 30, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

incidence of dose-limiting toxicity （DLT） [2 Years]
incidence and severity of DLT
incidence of adverse event（AE） [2 Years]
adverse events (AE)
Recommended dose for phase II trial RP2D [2 Years]
Recommended dose for phase II trial

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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