Clinical trial NCT06657144: A Study of CHS-114 in Combination With Toripalimab and/or Other Treatments in Participants With Advanced Solid Tumors
Official title: A Phase 1B, Multicenter, Open-Label Study of the Safety and Efficacy of CHS-114 in Combination With Toripalimab With or Without Other Treatments in Participants With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Solid Tumor
Advanced Solid Tumor
Keywords: Solid Tumors
Advanced Solid Tumors
Metastatic Solid Tumor
Cancer
Oncology
Tumor
CCR8
PD-1
Gastric cancer
Gastro-esophageal-junction (GEJ) cancer
Esophageal Adenocarcinoma (EAC)
Esophageal Squamous Cell Carcinoma
Cisplatin
5 Fluorouracil (5-FU)
Lead sponsor: Coherus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-24
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and preliminary efficacy of CHS-114 in combination with toripalimab and/or other standard of care (SOC) compound(s) in participants with advanced or metastatic solid tumors.


Eligibility criteria: Key Inclusion Criteria:

* At least 1 measurable lesion based on RECIST v1.1 as determined by the Investigator.
* Resolved acute effects of any prior therapy to baseline severity or Grade 1 in accordance with National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except for adverse events (AEs) not constituting a safety risk per Investigator judgement.

Cohort A (2L Gastric, Gastro-esophageal-junction \[GEJ\], Esophageal Adenocarcinoma \[EAC\]) Specific Inclusion Criteria:

* Histologically or cytologically documented unresectable, locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma that is human epidermal growth factor receptor 2 (HER2) - negative and microsatellite stable (MSS)/proficient mismatch repair (pMMR).
* Progressed during or after first line systemic therapy that includes a platinum and fluoropyrimidine doublet with or without anti-programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1)-directed therapy (that is, in the second line setting).
* Consent to provide tumor tissue samples (baseline and on-treatment) is required for enrollment.

Cohort B (2L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Inclusion Criteria:

* Histologically or cytologically documented unresectable, locally advanced or metastatic ESCC.
* Progressed during or after first line systemic therapy including a doublet of platinum and fluoropyrimidine or paclitaxel with or without anti-PD-1/PD-L1-directed therapy or anti-CTLA-4 and anti-PD-1/PD-L1-directed combination therapy.
* Consent to provide results from prior PD-L1 IHC assay score by FDA-approved or equivalent PD-L1 IHC diagnostic tests.
* Consent to provide archival tumor tissue sample (baseline) is required for enrolment.

Cohort C (1L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Inclusion Criteria:

* Histologically or cytologically documented unresectable, locally advanced or metastatic ESCC.
* Consent to provide baseline tumor tissue is required.
* Consent to provide results from prior PD-L1 IHC assay score by FDA-approved or equivalent PD-L1 IHC diagnostic tests.
* Calculated creatinine clearance ≥60 mL/min.

Key Exclusion Criteria:

* History of prior malignancy other than the cancer under study that is progressing or has required active treatment within the past 3 years.
* Symptomatic or untreated central nervous system metastases, including leptomeningeal metastases, requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids.
* Major surgery requiring general anesthesia within 28 days prior to the first dose of study treatment, still recovering from prior surgery, or with surgery scheduled during the study.
* Prior exposure to anti-C-C motif chemokine receptor 8 (CCR8) antibody.
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody (mAb) therapy or any excipient in the study treatment.
* Active uncontrolled bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
* Any condition that, in the opinion of the Investigator or Sponsor, would interfere with the interpretation of study results.

Cohort A (2L Gastric, Gastro-esophageal-junction \[GEJ\], Esophageal Adenocarcinoma \[EAC\]) Specific Exclusion Criteria:

* Received ≥ 2 prior systemic anticancer therapies for advanced or metastatic disease.
* Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).

Cohort B (2L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Exclusion Criteria:

* Received ≥ 2 prior systemic anticancer therapies for advanced or metastatic disease.
* Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).

Cohort C (1L Esophageal Squamous Cell Carcinoma \[ESCC\]) - Specific Exclusion Criteria:

* Received ≥ 1 prior systemic anticancer therapies for advanced or metastatic disease.
* Participants who progressed during or within 6 months following the last dose of neoadjuvant, or perioperative therapy with curative intent.
* Participants at high risk for developing esophageal fistula by clinical assessment or imaging, such as prior history or associated symptoms of esophageal fistula or T4 classification assessed by endoscopic ultrasound (EUS).
* Known dihydropyrimidine dehydrogenase deficiency or thymidine synthase gene polymorphism predisposing the participant to 5-FU toxicity.
* Known allergies to 5-FU or cisplatin.

Note: Other protocol-specified inclusion/exclusion criteria apply.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug until 90 days after the last dose of study drug (up to approximately 2.25 years)
Secondary outcomes:
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Investigator Assessment
timeFrame: Up to approximately 2.25 years
measure: Duration of Response (DOR) Per RECIST v1.1 Based on Investigator Assessment
timeFrame: Up to approximately 2.25 years
measure: Disease Control Rate (DCR) Per RECIST v1.1 Based on Investigator Assessment
timeFrame: Up to approximately 2.25 years
measure: Progression-free Survival (PFS) Per RECIST v1.1 Based on Investigator Assessment
timeFrame: Up to approximately 2.25 years
measure: Landmark PFS Rates
timeFrame: Months 6, 9, and 12
measure: Maximum Observed Serum Concentration (Cmax) of CHS-114
timeFrame: Up to approximately 2.25 years (pre-infusion and up to 336 hours post-infusion)
measure: Time to Reach Cmax (Tmax) of CHS-114
timeFrame: Up to approximately 2.25 years (pre-infusion and up to 336 hours post-infusion)
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of CHS-114
timeFrame: Up to approximately 2.25 years (pre-infusion and up to 336 hours post-infusion)
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Up to approximately 2.25 years
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Ochsner Health
state: Louisiana
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
References: