Status:
COMPLETED
Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors
Lead Sponsor:
Coherus Oncology, Inc.
Collaborating Sponsors:
Merck Sharp & Dohme LLC
Conditions:
Advanced Solid Tumor
Clear Cell Renal Cell Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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 t...
Detailed Description
This is a Phase 1/1b, open-label, first-in-human (FIH), dose-escalation and expansion study of CHS-388, a monoclonal antibody targeting IL-27, as a monotherapy and in combination in patients with soli...
Eligibility Criteria
Inclusion
- Part A and Part B Abbreviated
- ≥ 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
- Patients with NSCLC must have demonstrated progressive disease during or after the most recent treatment regimen
- Part C Abbreviated
- ≥ 18 years of age
- Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy OR histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
- Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
- At least 1 measurable lesion per RECIST 1.1
- Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
- ECOG performance status of 0-1
- ANC ≥1500/µL (1.5 x 109/L)
- Platelets ≥100 000/µL (≥ 100 x 109/L)
- Hemoglobin for participants with RCC: ≥9.0 g/dL; for participants with HCC: ≥8.5 g/dL
- Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
- Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
- International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
- Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
- Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or Part B:
- Progressed on CHS-388 by RECIST 1.1
- Did not experience prior Grade ≥ 3 toxicity related to CHS-388
- Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
- Has received no systemic anticancer therapies between CHS-388 doses
- Part C Abbreviated Inclusion Criteria specific to NSCLC Patients:
- No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
- Part A and Part B Abbreviated
Exclusion
- 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
- Part C Abbreviated
Key Trial Info
Start Date :
April 22 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 5 2025
Estimated Enrollment :
145 Patients enrolled
Trial Details
Trial ID
NCT04374877
Start Date
April 22 2020
End Date
June 5 2025
Last Update
November 10 2025
Active Locations (23)
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1
City of Hope
Duarte, California, United States, 91010
2
University of Southern California (USC) - Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
3
UCSF Medical Center - Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94143
4
University of Miami Leonard M. Miller School of Medicine (UMMSM)
Miami, Florida, United States, 33136