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

Phase 1

Not yet recruiting

• Conditions: Stage IV NSCLC
• Interventions: Drug: Poly ICLC; Drug: IVIG

• Registration Number: NCT06064279
• Lead Sponsor: VA Office of Research and Development

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 patien...

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 inter...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2023-09-01
• Study First Submitted QC: 2023-09-28
• Study First Posted: 2023-10-03
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-26
• Last Update Posted: 2024-04-30
• Study Start: 2024-06-24
• Primary Completion: 2026-06-22
• Study Completion: 2028-04-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 16

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Poly-ICLC + IVIG	IVIG	Patients with stage IV NSCLC will be treated with poly-ICLC + IVIG
Poly-ICLC + IVIG	Poly ICLC	Patients with stage IV NSCLC will be treated with poly-ICLC + IVIG

Primary Outcome Measures

Name	Time	Method
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	Ten months	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.

Secondary Outcome Measures

Name	Time	Method
To assess the percent of patients with increase PD-L1 expression and assess clinical outcome after treatment	Ten months	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.

Trial Locations

Locations (1)

Michael E. DeBakey VA Medical Center, Houston, TX; 🇺🇸 Houston, Texas, United States