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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: JS015; Biological: Paclitaxel; Drug: Irinotecan; Biological: Toripalimab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Leucovorin; Drug: Gemcitabine; Drug: Albumin-Bound Paclitaxel; Biological: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jiangnian Liu, PM; Phone Number: +86 18733176288; Email: jiangnian_liu@junshipharma.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Recruiting
      • Shanghai East Hospital
      • Contact: Jin Li, MD; Phone Number: 86 021-38804518; Email: lijin@csco.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who meet the following criteria for each indication cohort:

1. 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;
2. 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;
3. 1L gastric cancer cohort, patients with histologically or cytologically confirmed gastric/gastroesophageal junction adenocarcinoma with HER2-negative results and no prior systemic antitumor therapy;
4. 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;
5. 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:

1. Leptomeningeal metastases and /or active brain metastases;
2. Pleural, peritoneal, or pericardial effusion with clinical symptoms or requiring repeated management (puncture, drainage, etc.);
3. History of interstitial lung disease or a previous history of noninfectious pneumonia with corticosteroid therapy, or evidence of active pneumonia on screening imaging;
4. History of immunodeficiency;
5. History of serious cardiovascular and/or cerebrovascular diseases;
6. History of abdominal or tracheo-esophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months before the first dose of administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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.; 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.; Biological: Bevacizumab; Bevacizumab of 5mg/kg will be administered intravenously (IV) on days 1 and 15 every 28 day cycle, or7.5mg/kg on day 1 every 21 day cycle, based on different combined chemotherapy.
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.

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Collaborators: Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): January 28, 2026

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antidotes; Vitamin B Complex; Vitamins; Capecitabine; Oxaliplatin; Bevacizumab; Irinotecan; Albumin-Bound Paclitaxel; Gemcitabine; Fluorouracil; Leucovorin; Paclitaxel
• Other Study ID Numbers: JS015-002-Ib/II-GI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No