Study to Evaluate Safety and PK of CHS-006 in Combination With Toripalimab in Patients With Advanced Solid Tumors

A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CHS-006, as Monotherapy and in Combination With Toripalimab, in Participants With Advanced Solid Tumors

This phase 1 open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of CHS-006 in combination with toripalimab in 2 phases. Phase 1 (Dose Optimization phase) will explore 2 different dose combinations in participants with advanced/metastatic solid tumors (except pancreatic) and Phase 2 (Indication-specific Expansion phase) will use one selected dose in specific tumor types (non-small cell lung cancer-non squamous [NSCLC-NS] and Hepatocellular carcinoma [HCC])

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma; Non-Small Cell Lung Cancer; Advanced Solid Tumor
• Intervention / Treatment: Drug: CHS-006 (anti-TIGIT); Drug: toripalimab (anti-PD-1)

Detailed Description

The Dose Optimization phase will enroll participants with advanced/metastatic solid tumors (except pancreatic). Up to 20 participants will be randomized into two dosing arms. Two different primary advanced solid tumors have been selected for investigation of antitumor activity in the Indication-specific Expansion phase. Up to 40 participants will be enrolled into each Indication-specific Expansion phase cohort. All participants in both phases will receive CHS-006 in combination with toripalimab intravenously (IV) every 3 weeks (Q3W).

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Institute for Cancer
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females, ≥18 years old;
• Histopathologically or cytologically confirmed advanced solid tumor (except pancreatic) with disease progression after at least 1 prior line of standard therapy (Dose Optimization phase);
• Tumor-specific criteria (Indication-specific Expansion phase):
• NSCLC-NS (without sensitizing EGFR/ALK/ROS-1/MET mutations) 2nd line plus (2L+): has received and progressed on at least 1 prior chemotherapy regimen. Prior treatment with both anti-PD-1 therapy and platinum-based chemotherapy either concurrently or sequentially are eligible.
• Hepatocellular carcinoma (HCC) 2L+: has received and progressed on at least 1 prior anticancer regimen. Participants with prior treatment with an anti-PD-1 or PD-L1 agent are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and expected survival ≥12 weeks;
• At least 1 measurable lesion per RECIST v1.1;
• Adequate organ and marrow function

Exclusion Criteria:

• Current or prior use of systemic anticancer therapy, including but not limited to chemotherapy, immunotherapy, biologic therapy, hormone therapy, and targeted therapy, within 28 days prior to the 1st dose of CHS-006;
• NSCLC participants with genomic mutations (e.g., EGFR, ALK, ROS-1, MET, etc.) for which FDA-approved targeted therapies are available or require progression on appropriate prior to enrollment;
• Prior exposure to monoclonal antibodies (mAbs) targeting TIGIT or any of its ligands, including CD155, CD112, or CD113;
• Major surgery within 28 days prior to the 1st dose of CHS-006 or still recovering from prior surgery;
• Symptomatic or untreated central nervous system (CNS) metastases;
• Use of therapeutic immunosuppressive medication within 28 days prior to the 1st planned dose of CHS-006;
• Receipt of live, attenuated vaccination within 30 days prior to the 1st dose of CHS- 006;
• History of active autoimmune disease within the past 2 years, with the following exceptions: vitiligo, alopecia, endocrinopathies controlled by hormone replacement therapy, rheumatoid arthritis and other arthropathies that have not required immunosuppression other than nonsteroidal anti-inflammatory agents, celiac disease controlled by diet, or psoriasis controlled with topical medication;
• Participants with another active solid tumor that has not been curatively treated.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dose Optimization Phase - Arm A; Advanced solid tumor participants will receive CHS-006 in combination with toripalimab Q3W	Drug: CHS-006 (anti-TIGIT); Arm A participants will receive CHS-006 administered via IV Q3W.; Other Names: JS006; Drug: toripalimab (anti-PD-1); Arm B participants will receive toripalimab administered via IV Q3W.; Other Names: CHS-007, TAB001, JS001
Active Comparator: Dose Optimization Phase - Arm B; Advanced solid tumor participants will receive CHS-006 in combination with toripalimab Q3W	Drug: CHS-006 (anti-TIGIT); Arm A participants will receive CHS-006 administered via IV Q3W.; Other Names: JS006; Drug: toripalimab (anti-PD-1); Arm B participants will receive toripalimab administered via IV Q3W.; Other Names: CHS-007, TAB001, JS001
Active Comparator: Indication-specific Expansion Phase - Cohort 1 NSCLC-NS; NSCLC-NS participants will receive CHS-006 in combination with toripalimab Q3W	Drug: CHS-006 (anti-TIGIT); Arm A participants will receive CHS-006 administered via IV Q3W.; Other Names: JS006; Drug: toripalimab (anti-PD-1); Arm B participants will receive toripalimab administered via IV Q3W.; Other Names: CHS-007, TAB001, JS001
Active Comparator: Indication-specific Expansion Phase - Cohort 2 HCC; HCC participants will receive CHS-006 in combination with toripalimab Q3W	Drug: CHS-006 (anti-TIGIT); Arm A participants will receive CHS-006 administered via IV Q3W.; Other Names: JS006; Drug: toripalimab (anti-PD-1); Arm B participants will receive toripalimab administered via IV Q3W.; Other Names: CHS-007, TAB001, JS001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the number of participants with treatment-emergent adverse events (TEAEs) receiving CHS-006 administered in combination with toripalimab	Assessed by number of participants with TEAEs assessed by the investigator as per CTCAE v5.0.	Day 1 of study treatment through up to 90 days post last dose of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the PK profile of CHS-006 in combination with toripalimab	Assessed by serum concentration of CHS-006 and toripalimab as determined by validated assays	Measured at multiple timepoints from Day 1 of study treatment through up to 90 days post last dose of study treatment
Immunogenicity of CHS-006 and/or toripalimab	Percentage of participants who develop treatment-emergent antidrug antibodies (ADA) to CHS-006 and/or toripalimab	Measured at multiple timepoints from Day 1 of study treatment through up to 90 days post last dose of study treatment
Objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 assessed by the investigator	Investigator-assessed ORR as per RECIST v1.1	Measured at multiple timepoints from Day 1 of study treatment through +/- 7 days at the completion of or premature withdrawal from the study
Duration of response (DoR) using RECIST v1.1 assessed by the investigator	Investigator-assessed DoR as per RECIST v1.1	Measured at multiple timepoints from Day 1 of study treatment through +/- 7 days at the completion of or premature withdrawal from the study
Disease control rate (DCR) using RECIST v1.1 assessed by the investigator	Investigator-assessed DCR as per RECIST v1.1	Measured at multiple timepoints from Day 1 of study treatment through +/- 7 days at the completion of or premature withdrawal from the study
Time to response (TTR) using RECIST v1.1 assessed by the investigator	Investigator-assessed TTR as per RECIST v1.1	Measured at multiple timepoints from Day 1 of study treatment through +/- 7 days at the completion of or premature withdrawal from the study
Progression-free survival (PFS) using RECIST v1.1 assessed by the investigator	Investigator-assessed PFS as per RECIST v1.1	Measured at multiple timepoints from Day 1 of study treatment through +/- 7 days at the completion of or premature withdrawal from the study
Overall survival (OS) using RECIST v1.1 assessed by the investigator	Investigator-assessed PFS as per RECIST v1.1	Measured at multiple timepoints from Day 1 of study treatment through +/- 7 days at the completion of or premature withdrawal from the study

Collaborators and Investigators

• Sponsor: Coherus Biosciences, Inc.
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.; Medpace, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 2, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Solid Tumor; PD-1 inhibitor; TIGIT inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: CHS-006-01

Drug and device information, study documents

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