Clinical trial NCT04977453: GI-101 As a Single Agent or in Combination with Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors
Official title: A Phase 1/2, Open-label, Dose-escalation, and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101 As a Single Agent and in Combination with Pembrolizumab, Lenvatinib or Local Radiotherapy in Patients with Advanced or Metastatic Solid Tumors (Keynote B59)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Non-small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Renal Cell Carcinoma
Urinary Bladder Cancer
Melanoma
Sarcoma
Microsatellite Stable Colorectal Carcinoma
Merkel Cell Carcinoma
Esophageal Squamous Cell Carcinoma
Cervical Cancer
Vaginal Cancer
Vulvar Cancer
Keywords: GI-101/GI-101A
CD80-IgG4 Fc-IL2 variant
Immunotherapy
IL-2
Interleukin-2
Pembrolizumab
Lenvatinib
Radiotherapy
Lead sponsor: GI Innovation, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-07-27
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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)

Eligibility 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

Primary outcomes:
measure: Incidence and nature of Dose-Limiting Toxicity (DLTs)
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs)
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Objective Response Rate (ORR) according to RECIST version 1.1
timeFrame: Study Day 1, assessed up to approximately 24 months
Secondary outcomes:
measure: Peak plasma concentration (Cmax) of GI-101/GI-101A
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Half-life of GI-101/GI-101A (T1/2)
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Area under the plasma concentration versus time curve (AUC) of GI-101/GI-101A
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Disease control rate (DCR) according to RECIST version 1.1
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Duration of objective Response (DoR) according to RECIST version 1.1
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Time to Tumor Response (TTR) according to RECIST version 1.1
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Progression-Free Survival (PFS) according to RECIST version 1.1
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: ORR per iRECIST guidelines
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: DCR per iRECIST guidelines
timeFrame: Study Day 1, assessed up to approximately 24 months
Other outcomes:
measure: Incidence of anti-GI-101/GI-101A antibody (ADA) and neutralizing antibody (Nab)
timeFrame: Study Day 1, assessed up to approximately 24 months
measure: Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points
timeFrame: Study Day 1, assessed up to approximately 24 months
Locations:
city: New York
country: United States
facility: Tisch Cancer Institute (TCI), Icahn School of Medicine
state: New York
city: Huntersville
country: United States
facility: Carolina Biooncology Institute
state: North Carolina
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
state: Kyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Seongbuk-gu
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: GI Innovation
name: Nari Yun, PhD
role: STUDY_DIRECTOR
References: