Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors

NCT04374877 | Completed Phase 1 FDA Drug

• 3 other identifiers: SRF388-101KEYNOTE-C16MK-3475-C16
• Study Type: interventional
• Target: 145
• Locations: 3 countries
• Sites: 23

Brief Summary

This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of CHS-388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.

Conditions

Advanced Solid Tumor; Clear Cell Renal Cell Carcinoma; Hepatocellular Carcinoma; Non-small Cell Lung Cancer

Keywords

metastatic solid tumors; advanced solid tumors; Phase 1; CHS-388; IL-27; safety; efficacy; immunotherapy; cancer; immuno-oncology; kidney cancer; renal cell carcinoma; liver cancer; hepatocellular carcinoma; non-small cell lung cancer; pembrolizumab; PD-1; toripalimab; SRF388

Outcome Measures

Primary Outcomes (6)

• [Part A] Dose Limiting Toxicity (DLT)

  Evaluation of DLT of CHS-388 as a monotherapy.

  Assessed during first 28 days of treatment

• [Part B] Confirmed objective response rate (ORR)

  ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR per RECIST v1.1 and iRECIST.

  Up to 24 months

• [Part C] DLT

  Evaluation of DLT of CHS-388 in combination with pembrolizumab.

  Assessed during first 21 days of treatment

• [Part C] Summary of adverse events (AEs) based on treatment emergent AEs (TEAEs)

  Safety and tolerability of CHS-388 + pembrolizumab will be assessed by summarizing AEs and will be based on TEAEs. A TEAE is an AE that emerges or worsens in the period from the first dose of study treatment to 30 days after the last dose of study drug assessed by per CTCAE version 5.0 or higher.

  Up to 24 months

• [Part C -NSCLC Cohort] Objective response rate (ORR)

  ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR per RECIST v1.1 and iRECIST.

  Up to 24 months

• [Part D] Objective response rate (ORR)

  CR or PR per RECIST v1.1

  Up to 24 months

Secondary Outcomes (13)

• [Part A, Part B] Safety Analysis: Summary of adverse events (AEs) and based on treatment-emergent AEs (TEAEs)

  Up to 24 months

• [Part A, Part B, Part C] Pharmacokinetics (PK) of CHS-388

  Up to 24 months

• [Part D] Pharmacokinetics (PK) of CHS-388 and toripalimab

  Up to 24 months

• [Part A, Part B] Pharmacodynamics of CHS-388 (pSTAT levels)

  Up to 24 months

• [Part A, Part C] Objective response rate (ORR)

  Up to 24 months

Study Arms (4)

Part A Monotherapy Dose Escalation

EXPERIMENTAL

The Part A monotherapy dose escalation portion of the study will evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of CHS-388 as monotherapy in up to 30 patients with advanced solid tumors.

Drug: CHS-388

Part B CHS-388 Monotherapy Expansion

EXPERIMENTAL

Part B monotherapy expansion will evaluate the safety, tolerability, PK, pharmacodynamics, and efficacy of CHS-388 monotherapy at the recommended phase 2 dose (RP2D) in up to 40 patients with ccRCC, up to 40 patients with HCC, and up to 40 patients with NSCLC.

Drug: CHS-388

Part C CHS-388 in Combination with Pembrolizumab

EXPERIMENTAL

Part C will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with pembrolizumab in patients with advanced RCC or HCC, or anti-PD(L)1 relapsed/refractory advanced NSCLC.

Drug: CHS-388; Drug: Pembrolizumab

Part D CHS-388 in Combination with Toripalimab

EXPERIMENTAL

Part D will evaluate the safety, preliminary efficacy, tolerability, and PK of CHS-388 in combination with toripalimab in patients with anti-PD(L)1 relapsed/refractory advanced NSCLC.

Drug: CHS-388; Drug: Toripalimab

Interventions

CHS-388 DRUG

CHS-388 is a fully human IgG1 antibody against IL-27. Inhibition of IL-27 with CHS-388 reduces STAT1 phosphorylation leading to increased pro-inflammatory (anti-tumor) cytokine secretion (e.g., IFN-g, TNF-a) and decreased expression of inhibitory immune checkpoint receptors (e.g., PD-L1, TIGIT, LAG3) on immune cells that may result in anticancer therapeutic activity.

Also known as: Casdozokitug

Part A Monotherapy Dose Escalation; Part B CHS-388 Monotherapy Expansion; Part C CHS-388 in Combination with Pembrolizumab; Part D CHS-388 in Combination with Toripalimab

Pembrolizumab DRUG

Pembrolizumab by intravenous (IV) infusion

Also known as: Keytruda®

Part C CHS-388 in Combination with Pembrolizumab

Toripalimab DRUG

Toripalimab by IV infusion

Also known as: Loqtorzi®

Part D CHS-388 in Combination with Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy, and for whom no available therapies are appropriate (based on investigator judgment)
• Patients in Part B with advanced or metastatic ccRCC, HCC, or NSCLC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
• Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization \[TACE\]) or Stage C
• For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
• For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
• For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
• Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) \< 2.5 x ULN (\< 5 x ULN if liver metastasis or for patients with HCC)
• For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
• Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC

You may not qualify if:

• Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
• For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
• For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
• History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
• Major surgery within 4 weeks prior to Screening
• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
• Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
• No prior systemic therapy for unresectable or metastatic disease
• Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
• For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
• For patients with HCC, moderate or severe ascites
• For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
• For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
• History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs

Sponsors & Collaborators

• Coherus Oncology, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (23)

City of Hope

Duarte, California, 91010, United States

Location

University of Southern California (USC) - Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCSF Medical Center - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

University of Miami Leonard M. Miller School of Medicine (UMMSM)

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System (UMHS)

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine - St. Louis

St Louis, Missouri, 63110, United States

Location

Roswell Park

Buffalo, New York, 14263, United States

Location

Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Sciences Center (OUHSC) - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center (University of Pittsburgh Cancer Institute (UPCI))

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University Medical Center (VUMC)

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Center Singapore (NCCS)

Singapore, 169610, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Neoplasms; Kidney Neoplasms; Liver Neoplasms

Interventions

pembrolizumab; toripalimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Koho Iizuka, MD

  Coherus BioSciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 5, 2020
• Study Start: April 22, 2020
• Primary Completion: May 28, 2025
• Study Completion: June 5, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); KR (3); SG (2)