A Study to Evaluate the Safety and Therapeutic Activity of GI-102 As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced Solid Tumors (KEYNOTE-G08)

Phase 2RecruitingNCT05824975

GI Innovation, Inc.358 enrolled

Overview

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(T-DXd) over a range of advanced and/or metastatic solid tumors.

This is a phase 1/2, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, and anti-tumor effect of GI-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(T-DXd) over a range of advanced and/or metastatic solid tumors. This study is adaptive in nature. The study is composed of four parts: * Part A: Dose escalation and optimization phase of GI-102 intravenous (IV) monotherapy * Part A dose escalation phase * Part A dose optimization phase: Dose optimization cohorts in patients with 2L+, CPI-refractory metastatic melanoma * Part B: Dose escalation and expansion phase of GI-102 subcutaneous (SC) monotherapy * Part C: Indication specific cohorts of GI-102 IV in combination with conventional anti-cancer drugs or trastuzumab deruxtecan (T-DXd) * Part D: Indication specific cohorts of GI-102 IV in combination with pembrolizumab GI-102 is a novel bi-specific Fc fusion protein containing the CD80 ectodomain as an N-terminal moiety and an interleukin (IL)-2 variant as a C-terminal moiety configurated via a human immunoglobulin G4 (IgG4) Fc. GI-102 has unique characteristics by having bispecificity to CD80 and IL2Rβγ. The CD80 portion is responsible for targeting tumor/immune cells while blocking CTLA-4 expressed on the Treg cells. The IL-2v of GI-102 is designed to abolish IL-2Rα affinity and therefore minimize the effect on Treg while it has very outstanding effect on NK and CD8 T cell proliferation and activity through IL-2Rbr affinity.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

GI-102 subcutaneous (SC)DRUG

0.12 mg/kg, 0.24 mg/kg or Recommended phase 2 dose of GI-102 will be administered via SC injection Q3W up to 2 years (approximately 35 years).

GI-102DRUG

Dose level will be escalated from 0.06 mg/kg to 0.45 mg/kg and Recommended phase 2 dose (or RP2D-1, RP2D+1) of GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).

doxorubicinDRUG

Doxorubicin will be administered intravenously at a dose of 75 mg/m2 on Day 3 every 3-week (21-day) cycle for up to 6 cycles.

paclitaxelDRUG

Paclitaxel will be administered intravenously over 1 hour at a dose of 80 mg/m2 each time weekly as a diluted solution according to the prescribing information.

bevacizumabDRUG

Bevacizumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks.

eribulinDRUG

Eribulin will be administered intravenously at a dose of over 1.4 mg/m2 over 2 to 5 minutes on Days 3 and 10 every 3-week (21-day) cycle.

trastuzumab deruxtecan (T-DXd)DRUG

T-DXd will be administered initially as a 5.4 mg/kg (or 6.4 mg/kg only for gastric cancer) IV over 30 - 90 minutes every 3 weeks.

pembrolizumabDRUG

pembrolizumab will be administered at a dose of 200 mg as IV infusion Q3W.

GI-102DRUG

Recommended phase 2 dose (or RP2D-1, RP2D-2) of GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening. * Has adequate organ and marrow function as defined in protocol. * Measurable disease as per RECIST v1.1. * ECOG performance status 0-1. * Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy. * HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol. Key Exclusion Criteria: * Has known active CNS metastases and/or carcinomatous meningitis. * An active second malignancy. * Has active or a known history of Hepatitis B or known active Hepatitis C virus infection. * Has active tuberculosis or has a known history of active tuberculosis. * Active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration. * History of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis. * Has an active autoimmune disease that has required systemic treatment in past 2 years. * Previous immunotherapies related to mode of action of GI-102. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1. * Administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment. * Radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy. * Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1. * Known hypersensitivity to any of the components of the drug products and/or excipients of GI-102. Other protocol defined inclusion exclusion criteria may apply

Locations (11)

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, United States

RECRUITING

Mayo Clinic in Minnesota

Rochester, Minnesota, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

RECRUITING

Seoul National University Hospital

Seoul, Seoul, South Korea

RECRUITING

St. Vincent's Hospital

Suwon, suwon, South Korea

RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, South Korea

RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

...and 1 more locations

Outcomes

Primary Outcomes

Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose escalation phase of Part A and B)

A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during dose escalation and dose expansion, and is considered by the Investigator to be related to GI-102.

Time frame: Study Day 1, assessed up to DLT period (3 weeks after treatment)

Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) (dose escalation phase of Part A and B)

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Time frame: Study Day 1, assessed up to approximately 24 months

Objective Response Rate (ORR) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)

ORR is defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).

Time frame: Study Day 1, assessed up to approximately 24 months

Secondary Outcomes

Objective Response Rate (ORR) (dose escalation phase of Part A and B)

Time frame: Study Day 1, assessed up to approximately 24 months

Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)

Time frame: Study Day 1, assessed up to DLT period (3 weeks after treatment)

Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) (dose optimization phase of Part A, dose expansion phase of Part B, Part C and D)

Time frame: Study Day 1, assessed up to approximately 24 months

Disease Control Rate (DCR)

DCR is defined as the percentage of patients who have achieved CR, PR and stable disease (SD), per RECIST v1.1 guideline as determined by the investigators.

Time frame: Study Day 1, assessed up to approximately 24 months

Duration of objective response (DoR)

DCR is defined as the time from the first occurrence of a documented objective response to the time of the first document disease progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.

Time frame: Study Day 1, assessed up to approximately 24 months

Progression-free survival (PFS)

PFS is defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per RECIST v1.1 guideline as determined by the investigator

Time frame: 6-month, 12-month, and 18-month

Overall survival (OS)

OS is defined as the time from the first study treatment to death from any cause

Time frame: 12-month and 18-month

Peak plasma concentration (Cmax) of GI-102

Based on the concentration vs time profile by dose level

Time frame: Study Day 1, assessed up to approximately 24 months

Half-life of GI-102 (T1/2)

Based on the concentration vs time profile by dose level

Time frame: Study Day 1, assessed up to approximately 24 months

Area under the plasma concentration versus time curve (AUC) of GI-102

Based on the concentration vs time profile by dose level

Time frame: Study Day 1, assessed up to approximately 24 months

Clearance of GI-102

Based on the concentration vs time profile by dose level

Time frame: Study Day 1, assessed up to approximately 24 months

Volume of distribution (Vd) of GI-102 after administration

Based on the concentration vs time profile by dose level

Time frame: Study Day 1, assessed up to approximately 24 months

A Study to Evaluate the Safety and Therapeutic Activity of GI-102 As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced Solid Tumors (KEYNOTE-G08)

Overview

Conditions

Interventions

Eligibility

Locations (11)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts