Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC (HAITEN-ICI)
Study Overview
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
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030-4211
- Michael E. DeBakey VA Medical Center, Houston, TX
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Poly-ICLC + IVIG
Patients with stage IV NSCLC will be treated with poly-ICLC + IVIG
|
Tol like receptor 3 agonist
Other Names:
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
Time Frame: 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.
|
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
Time Frame: 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.
|
Ten months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Farrah Kheradmand, MD, Michael E. DeBakey VA Medical Center, Houston, TX
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
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)?
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
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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