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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)

ConditionsAdvanced Solid TumorMetastatic Solid TumorSoft Tissue Sarcoma (STS)Platinum-resistant Ovarian Cancer (PROC)Hepatocellular Carcinoma (HCC)Colorectal Cancer (CRC)HER2 Negative Breast CancerCutaneous MelanomaRenal Cell Carcinoma (RCC)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGI Innovation, Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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-102

    Drug

    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).

  • doxorubicin

    Drug

    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.

  • paclitaxel

    Drug

    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.

  • bevacizumab

    Drug

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

  • eribulin

    Drug

    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.

  • pembrolizumab

    Drug

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

  • GI-102

    Drug

    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).

Treatment groups

358 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: GI-102Experimental treatment 1 intervention
Group B: GI-102 subcutaneous (SC)Experimental treatment 1 intervention
Group C: GI-102 + doxorubicinExperimental treatment 2 interventions
Group D: GI-102 + paclitaxel + bevacizumabExperimental treatment 3 interventions
Group E: GI-102 + eribulinExperimental treatment 2 interventions
Group F: GI-102 + trastuzumab deruxtecan (T-DXd)Experimental treatment 2 interventions
Group G: GI-102 + pembrolizumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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)
2

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
3

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

1

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

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
2

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

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)
3

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)

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
4

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

Other outcomes

1

Incidence of anti-GI-102 antibody (ADA) and neutralizing antibody (Nab)

Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.

Time frame
Study Day 1, assessed up to approximately 24 months
2

Immunophenotyping of peripheral blood CD4+ T cells

CD4+ T cells in peripheral blood will be assessed by flow cytometry at various time points

Time frame
Study Day 1, assessed up to approximately 24 months
3

Immunophenotyping of peripheral blood CD8+ T cells

CD8+ T cells in peripheral blood will be assessed by flow cytometry at various time points

Time frame
Study Day 1, assessed up to approximately 24 months
4

Immunophenotyping of peripheral blood Treg cells

Treg cells in peripheral blood will be assessed by flow cytometry at various time points

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

GI Innovation, Inc.

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Source ClinicalTrials.gov
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