A Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of JS015 Combination Therapy in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- JS015
- Conditions
- Advanced Solid Tumor
- Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Enrollment
- 186
- Locations
- 1
- Primary Endpoint
- incidence of dose-limiting toxicity （DLT）
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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;
- •Life expectancy \>=12 weeks;
- •At least one measurable lesion according to RECIST 1.1;
- •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
Arms & Interventions
Cohort 1: esophogeal squamous carcinoma
In Cohort 1, patients will be treated with JS015 in combination with paclitaxel or irinotecan
Intervention: JS015
Cohort 1: esophogeal squamous carcinoma
In Cohort 1, patients will be treated with JS015 in combination with paclitaxel or irinotecan
Intervention: Paclitaxel
Cohort 1: esophogeal squamous carcinoma
In Cohort 1, patients will be treated with JS015 in combination with paclitaxel or irinotecan
Intervention: Irinotecan
Cohort 2: gastric cancer
In Cohort 2, patients will be treated with JS015 in combination with paclitaxel
Intervention: JS015
Cohort 2: gastric cancer
In Cohort 2, patients will be treated with JS015 in combination with paclitaxel
Intervention: Paclitaxel
Cohort 3: gastric cancer
In Cohort 3, patients will be treated with JS015 in combination with toripalimab and XELOX
Intervention: JS015
Cohort 3: gastric cancer
In Cohort 3, patients will be treated with JS015 in combination with toripalimab and XELOX
Intervention: Toripalimab
Cohort 3: gastric cancer
In Cohort 3, patients will be treated with JS015 in combination with toripalimab and XELOX
Intervention: Capecitabine
Cohort 3: gastric cancer
In Cohort 3, patients will be treated with JS015 in combination with toripalimab and XELOX
Intervention: Oxaliplatin
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: JS015
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: Irinotecan
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: Capecitabine
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: Oxaliplatin
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: Bevacizumab
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: Fluorouracil
Cohort 4: colorectal cancer
In Cohort 4, patients will be treated with JS015 plus bevacizumab in combination with XELOX or FOLFIRI
Intervention: Leucovorin
Cohort 5: pancreatic cancer
In Cohort 5, patients will be treated with JS015 in combination with toripalimab, albumin-bound paclitaxel and gemcitabine
Intervention: JS015
Cohort 5: pancreatic cancer
In Cohort 5, patients will be treated with JS015 in combination with toripalimab, albumin-bound paclitaxel and gemcitabine
Intervention: Toripalimab
Cohort 5: pancreatic cancer
In Cohort 5, patients will be treated with JS015 in combination with toripalimab, albumin-bound paclitaxel and gemcitabine
Intervention: Gemcitabine
Cohort 5: pancreatic cancer
In Cohort 5, patients will be treated with JS015 in combination with toripalimab, albumin-bound paclitaxel and gemcitabine
Intervention: Albumin-Bound Paclitaxel
Outcomes
Primary Outcomes
incidence of dose-limiting toxicity （DLT）
Time Frame: 2 Years
incidence and severity of DLT
incidence of adverse event（AE）
Time Frame: 2 Years
adverse events (AE)
Recommended dose for phase II trial RP2D
Time Frame: 2 Years
Recommended dose for phase II trial
Secondary Outcomes
- Peak concentration (Cmax)(2 years)
- time to peak concentration（Tmax）(2 years)
- elimination half life（t1/2）(2 years)
- immunogenicity(2 years)
- Objective response rate (ORR) based on Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1)(2 years)
- Progression free survival (PFS)(2 years)
- overall survival (OS)(2 years)