Clinical Trial Finder

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

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.

Arms

Experimental: GI-102

Dose escalation: GI-102 intravenous (IV), multiple ascending doses Dose optimization: GI-102 intravenous (IV), sRP2D Dose optimization: GI-102 intravenous (IV), sRP2D-1 (or sRP2D+1)

Experimental: GI-102 subcutaneous (SC)

Dose escalation: GI-102 subcutaneous (SC), multiple ascending doses Dose expansion: GI-102 subcutaneous (SC), sRP2D

Experimental: GI-102 + doxorubicin

Experimental: GI-102 + paclitaxel + bevacizumab

Experimental: GI-102 + eribulin

Experimental: GI-102 + trastuzumab deruxtecan (T-DXd)

Experimental: GI-102 + pembrolizumab

Interventions

Drug: - GI-102 subcutaneous (SC)

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).

Drug: - GI-102

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).

Drug: - doxorubicin

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.

Drug: - paclitaxel

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.

Drug: - bevacizumab

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

Drug: - eribulin

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.

Drug: - trastuzumab deruxtecan (T-DXd)

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.

Drug: - pembrolizumab

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

Drug: - GI-102

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).