Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC (HAITEN-ICI)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IV NSCLC
• Intervention / Treatment: Drug: Poly ICLC; Drug: IVIG

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Farrah Kheradmand, MD; Phone Number: (713) 791-1414; Email: Farrah.Kheradmand@va.gov
• Study Contact Backup: Name: Anita L Sabichi; Phone Number: (713) 791-1414; Email: Anita.Sabichi@va.gov

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030-4211
      • Michael E. DeBakey VA Medical Center, Houston, TX
      • Contact: Farrah Kheradmand, MD; Phone Number: 713-791-1414; Email: Farrah.Kheradmand@va.gov
      • Principal Investigator: Farrah Kheradmand, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Poly-ICLC + IVIG; Patients with stage IV NSCLC will be treated with poly-ICLC + IVIG	Drug: Poly ICLC; Tol like receptor 3 agonist; Other Names: Hiltonol; Drug: IVIG; pooled IVIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 o	Evaluate the safety 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.	Ten months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the percent of patients with increase PD-L1 expression and assess clinical outcome after treatment	To quantitate systemic immune responses in patients who receive intratumor IVIG + poly-ICLC, and IM poly-ICLC while receiving ICIs. Pt's adaptive immune cells (T cells) will be examined for the expression of activation markers before and after treatment. The correlation between % changes in immune cell activation and disease progression will be determined.	Ten months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Oncovir, Inc.
• Investigators: Principal Investigator: Farrah Kheradmand, MD, Michael E. DeBakey VA Medical Center, Houston, TX

Study record dates

Study Major Dates

• Study Start (Estimated): June 24, 2024
• Primary Completion (Estimated): June 22, 2026
• Study Completion (Estimated): April 4, 2028

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC, Immune Checkpoint inhibitor , PDL-1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Immunologic Factors; Interferon Inducers; Poly ICLC
• Other Study ID Numbers: SPLP-002-23S; CSR&D (Other Grant/Funding Number: VHA 1 IO1 CX002666-01)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No