Title
A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of GS-1811, an Afucosylated Anti-CCR8 Monoclonal Antibody, as Monotherapy and in Combination With an Anti PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors

Description
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as monotherapy and in combination with Zimberelimab in participants with advanced solid tumors.

This study will be conducted in 4 parts (Part A and Part B: monotherapy, Part C and Part D: combination therapy), in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit.

Objective
Primary:
-To evaluate the safety and tolerability and to determine the MTD and/or the RP2D of GS-1811 as monotherapy and in combination with ZIM in participants with advanced solid tumors
Secondary:
-To evaluate the PK and immunogenicity of GS-1811 as monotherapy and in combination with ZIM in participants with advanced solid tumors
-Part D: To evaluate preliminary efficacy of GS-1811 in combination with ZIM in participants with select advanced solid tumors

Treatment Experimental: Part A - GS-1811 Dose Escalation
Drug: GS-1811
Administered intravenously

Experimental: Part B - Mandatory Paired Tumor Biopsy
Drug: GS-1811
Administered intravenously

Experimental: Part C: GS-1811 + Zimberelimab dose escalation
Drug: GS-1811
Administered intravenously
Drug: Zimberelimab
Administered intravenously

Experimental: Part D: GS-1811 + Zimberelimab dose expansion
Drug: GS-1811
Administered intravenously
Drug: Zimberelimab
Administered intravenously

Key Eligibility Key Inclusion Criteria:

Disease


Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit

Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit

Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or whose disease is indicated for anti-PD-(L)1 monoclonal antibody monotherapy

Part D: Individuals with pathologically confirmed select advanced solid tumors.


Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Part D

Adequate organ function

Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception

Tissue requirement:


Part A, Part C, and Part D: Must provide pre-treatment adequate tumor tissue sample prior to enrolment

Part B: Must have fresh pre-treatment and on-treatment biopsy for biomarker analysis

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital