## Protocol Section
### Identification Module
**NCT ID:** NCT06064279

**Acronym:** HAITEN-ICI

**Brief Title:** Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC

**Official Title:** Harnessing Allo-immunity to Enhance Immune Checkpoint Inhibitor Responses in Advanced NSCLC

#### Organization Study ID Info
**ID:** SPLP-002-23S
#### Organization
**Class:** FED
**Full Name:** VA Office of Research and Development
#### Secondary ID Infos
**Domain:** VAMC
**ID:** CSR&D
**Type:** OTHER_GRANT
### Status Module
#### Completion Date
**Date:** 2028-04-04

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-26

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06-22

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-24

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2023-10-03
**Type:** ACTUAL
**Study First Submit Date:** 2023-09-01
**Study First Submit QC Date:** 2023-09-28
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Oncovir, Inc.

#### Lead Sponsor

**Class:** FED

**Name:** VA Office of Research and Development

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Stage IV NSCLC

**Keywords:**

- NSCLC, Immune Checkpoint inhibitor , PDL-1

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 16

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Drug: Poly ICLC

- Drug: IVIG

**Label:** Poly-ICLC + IVIG

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Poly-ICLC + IVIG

**Description:** Tol like receptor 3 agonist

**Name:** Poly ICLC

**Other Names:**

- Hiltonol

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Poly-ICLC + IVIG

**Description:** pooled IVIG

**Name:** IVIG

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** 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

#### Secondary Outcomes

**Description:** 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.

**Measure:** To assess the percent of patients with increase PD-L1 expression and assess clinical outcome after treatment

**Time Frame:** Ten months

### Eligibility Module

**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 Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Farrah.Kheradmand@va.gov

**Name:** Farrah Kheradmand, MD

**Phone:** (713) 791-1414

**Role:** CONTACT

**Contact 2:**

**Email:** Anita.Sabichi@va.gov

**Name:** Anita L Sabichi

**Phone:** (713) 791-1414

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Houston

**Contacts:**

***Contact 1:***

- **Email:** Farrah.Kheradmand@va.gov

- **Name:** Farrah Kheradmand, MD

- **Phone:** 713-791-1414

- **Role:** CONTACT

***Contact 2:***

- **Name:** Farrah Kheradmand, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Michael E. DeBakey VA Medical Center, Houston, TX

**State:** Texas

**Zip:** 77030-4211

#### Overall Officials

**Official 1:**

**Affiliation:** Michael E. DeBakey VA Medical Center, Houston, TX

**Name:** Farrah Kheradmand, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: NSCLC

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11172

- Name: Lung Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

### Intervention Browse Module - Ancestors

- ID: D000007369

- Term: Interferon Inducers

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M2342

- Name: Immune Checkpoint Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M280480

- Name: Poly ICLC

- Relevance: HIGH

- As Found: Colchicine

- ID: M10407

- Name: Interferons

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000019531

- Term: Poly ICLC

### Misc Info Module

- Version Holder: 2024-05-24
