GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors

GI Innovation

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Melanoma; Vaginal Cancer; Advanced Solid Tumor; Microsatellite Stable Colorectal Carcinoma; Merkel Cell Carcinoma; Urinary Bladder Cancer; Sarcoma; Vulvar Cancer; Non-small Cell Lung Cancer; Esophageal Squamous Cell Carcinoma; Renal Cell Carcinoma; Cervical Cancer; Metastatic Solid Tumor; Head and Neck Squamous Cell Carcinoma

Treatments: Radiation: Local Radiotherapy; Drug: GI-101A; Drug: Lenvatinib; Drug: GI-101; Drug: Pembrolizumab (KEYTRUDA®)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04977453

GII-101-P101 (MK-3475-B59)

KEYNOTE-B59 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy (RT) over a range of advanced and/or metastatic solid tumors.

Full description

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)

Enrollment: 430 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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430 participants in 6 patient groups

GI-101

Experimental group

Description:

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

Treatment:

Drug: GI-101

GI-101 + Pembrolizumab

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: GI-101

GI-101 + Lenvatinib

Experimental group

Description:

Dose optimization: Dose expansion:

Treatment:

Drug: GI-101

Drug: Lenvatinib

GI-101 + Local Radiotherapy

Experimental group

Description:

Dose optimization: Dose expansion:

Treatment:

Drug: GI-101

Radiation: Local Radiotherapy

GI-101A

Experimental group

Description:

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

Treatment:

Drug: GI-101A

GI-101A + Pembrolizumab

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: GI-101A