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-101.

• - 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 (except Part D).

• - 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-101, pembrolizumab or lenvatinib.

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-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib or local RT over a range of advanced and/or metastatic solid tumors. This study will comprise six parts.

• - Part A: Dose-escalation and expansion cohorts of GI-101 monotherapy.

• - Part B: Dose-escalation and expansion cohorts of GI-101 plus pembrolizumab.

• - Part C: Dose-optimization and expansion cohorts of GI-101 plus lenvatinib.

• - Part D: Dose-optimization and expansion cohorts of GI-101 plus local RT.

• - Part E: Dose-escalation and expansion cohorts of GI-101A monotherapy.

• - Part F: Dose-escalation and expansion cohorts of GI-101A plus pembrolizumab.

GI-101/GI-101A 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-101A is an abbreviation of advanced GI-101 with an improved formulation for manufacture consistency. Drug Information available for: Pembrolizumab (https://www.keytrudahcp.com), Lenvatinib (http://www.lenvima.com)

Arms

Experimental: GI-101

Dose escalation: GI-101, multiple ascending doses Dose expansion:

Experimental: GI-101 + Pembrolizumab

Dose escalation: GI-101, multiple ascending doses Dose expansion:

Experimental: GI-101 + Lenvatinib

Dose optimization: Dose expansion:

Experimental: GI-101 + Local Radiotherapy

Dose optimization: Dose expansion:

Experimental: GI-101A

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Experimental: GI-101A + Pembrolizumab

Dose escalation: GI-101A, multiple ascending doses Dose expansion:

Interventions

Drug: - GI-101

Recommended phase 2 dose of GI-101 will be administered via IV infusion Q3W up to 2 years (approximately 35 years).

Drug: - Pembrolizumab (KEYTRUDA®)

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

Drug: - Lenvatinib

Lenvatinib will be administered at an approved dose orally.

Radiation: - Local Radiotherapy

Patients will receive SBRT prior to the first dose of GI-101

Drug: - GI-101A

Recommended phase 2 dose of GI-101A will be administered via IV infusion Q3W up to 2 years (approximately 35 years).