Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC

NCT ID: NCT06064279

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-04
• Study Completion Date: 2024-06-04

Brief Summary

Veterans with advanced lung cancer may benefit from recent advances in technologies that is designed to change the activities of their own white blood cells and help kill tumors. However, many cancers can hide from white blood cells making white blood cells less effective in killing tumors. In this study the investigators plan to boost the activity of patients white blood cell by making tumor cells more visible to the white blood cells. This will be done by injecting antibodies and a new drug that together can make white blood cells inside tumors more active. The investigators plan to recruit sixteen people with advanced lung cancer to make sure that this treatment, which has not been done in any humans, is safe and well tolerated.

Detailed Description

This is a phase 1b, a first-in-humans, study to examine the safety and feasibility of administration of intratumor (IT) IVIG + poly-ICLC (Hiltonoll®), and intramuscular (IM) poly-ICLC (Hiltonoll®) for the treatment of advanced non-small cell lung cancer (NSCLC) in Veterans without targetable mutations. The investigators will employ the Bayesian optimal interval (BOIN) design 1, with dose escalation, de-escalation endpoints to find the maximum tolerated dose (MTD) in IT injections (IVIG + poly-ICLC) and IM poly-ICLC in 16 subjects while receiving front line Immune Checkpoint inhibitors (ICIs) as the standard of care (SOC). All patients continue to receive ICIs. If safe, a future phase II randomized-controlled study will be designed to determine if treatment with IT injections (IVIG + poly-ICLC) and IM injections (poly-ICLC) results in improved progression free survival.

Primary Objective: To evaluate the safety and determine the MTD as assessed by Common Terminology Criteria for Adverse Events version 6 (CTCAE v. 6) of IT injection of IVIG + poly-ICLC, and IM poly-ICLC given in combination with ICI in Veterans with stage IV NSCLC.

Secondary Objective: To quantitate systemic and tissue-specific immune responses in patients who receive intertumoral IVIG + poly-ICLC, and IM poly-ICLC while receiving ICIs.

Primary Endpoint: Assessment of an MTD dose for IT injection of IVIG + poly-ICLC, and IM injection of poly-ICLC given in combination with ICI in patients with stage IV NSCLC. The primary safety endpoint includes short term and long-term dose limiting toxicity (DLT), and observing less than 25% grade 3 toxicity.

Secondary Endpoints: 1) To assess the correlation of pre-therapy tumor PD-L1 expression with clinical benefit - All tumors will be assessed for PD-L1 expression prior to therapy initiation. 2) To determine the pre-treatment tumor immune infiltrate, and post treatment T cell activation, and correlation with treatment response.

Conditions

Stage IV NSCLC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Poly-ICLC + IVIG

Patients with stage IV NSCLC will be treated with poly-ICLC + IVIG

Group Type: EXPERIMENTAL

Poly ICLC

Intervention Type: DRUG

Tol like receptor 3 agonist

IVIG

Intervention Type: DRUG

pooled IVIG

Interventions

Poly ICLC

Tol like receptor 3 agonist

Intervention Type: DRUG

IVIG

pooled IVIG

Intervention Type: DRUG

Other Intervention Names

Hiltonol

Eligibility Criteria

Inclusion Criteria

• Veterans with advanced (stage IV) NSCLC
• Eligible to receive ICI/antiPD-1mAb
• No known mutation actionable for first line treatment
• An Eastern Cooperative Oncology Group (ECOG) performance-status (PS) score of 2 or less (ECOG PS is a 5-point scale in which higher scores reflect greater disability)

• Veterans' responses will be defined as eligible to enroll in HAITEN-ICIs if they meet all criteria
• To minimize the effects of immunosuppression on the ability to induce antitumor immunity, the investigators will recruit those who have not received systemic cytotoxic chemotherapy (e.g., platinum, taxane, pemetrexed, etc.), do not have major immunosuppression, and are not recipients of organ transplantation
• Based on our patient population at the MEDVAMC, the investigators estimate that ~30-40% of participants would be receiving systemic chemotherapy and ICIs concurrently, and ~60-70% will be receiving ICI monotherapy
• Therefore, the investigators anticipate no difficulty in meeting the recruitment goal of 16 persons at our center over two years and ~18 at each of the other sites over the 4-year study period

Exclusion Criteria

Veterans with

• Concurrent other malignancies, except for localized prostate or localized skin cancer
• Uncontrolled rheumatologic diseases (such as rheumatoid arthritis)
• Current usage of biologics or immunosuppressive therapies
• Status post organ transplant
• An acute respiratory illness (pneumonia, bronchitis, upper respiratory tract infection) in the preceding 4 weeks

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oncovir, Inc.

INDUSTRY

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Farrah Kheradmand, MD

Role: PRINCIPAL_INVESTIGATOR

Michael E. DeBakey VA Medical Center, Houston, TX

Locations

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Countries

United States

Other Identifiers

CSR&D

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SPLP-002-23S

Identifier Type: -

Identifier Source: org_study_id