Pembrolizumab + Poly-ICLC in MRP Colon Cancer

NCT ID: NCT02834052

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-10
• Study Completion Date: 2022-07-29

Brief Summary

The main purpose of this study is to determine the dose of poly-ICLC that is safe and tolerable when it is combined with pembrolizumab in patients with colon cancer. This study will also evaluate how the combination of pembrolizumab and poly-ICLC activates the immune system in the patient's blood and inside the tumor; how it affects the size and number of tumor(s) in each patient; and how effective the combination is in patients with colon cancer that is unlikely to respond to pembrolizumab alone.

Detailed Description

Mismatch repair genes normally serve to fix the small glitches that occur when DNA is copied as cells divide. In 1993, researchers discovered that mutations in human mismatch repair genes play a key role in the development of certain forms of colorectal cancer; individuals who are deficient in these mismatch repair genes are at high risk for colorectal cancer. Accumulating evidence has shown that immunotherapy may be most effective against these cancers.

Programmed cell death protein 1, also known as PD-1, functions as an immune checkpoint, down-regulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance. A new class of immunotherapy drugs that block PD-1, the PD-1 inhibitors, activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer.

Current clinical trials are showing that patients whose tumors are mismatch repair deficient are more likely to respond to immune-boosting anti-PD-1 drugs-such as pembrolizumab-than those with tumors proficient in mismatch repair. The idea is that the greater the number of DNA glitches in a tumor cell, the more abnormal proteins it will produce-and the more abnormal proteins that are generated, the greater the odds that the body's immune cells will regard the tumor cells as "foreign" and target them for destruction. Thus far, PD-1 inhibitors have shown great promise for mismatch repair deficient cancer patients, but not for mismatch repair proficient (MRP) cancer patients.

In this clinical trial, the investigators hypothesize that treating MRP colon cancer patients with immunostimulating agent poly-ICLC will generate an inflammatory response, increasing epitope recognition and development of tumor reactive T-cells at the tumor site. However, interferon alpha and gamma produced by the poly-ICLC will increase PD-L1 expression and limit new T-cell development. Thus, PD1 blockade will increase the effectiveness of treatment with pembrolizumab.

Conditions

Metastatic Colon Cancer; Solid Tumor

Study Design

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

Study Groups

Phase 1

This "Run In" phase is aimed to determine if poly-ICLC can be safely combined with standard dosages of pembrolizumab:

i. Pembrolizumab will be administered 200 mg intravenously (IV) every 3 weeks (q3w)

ii. Poly-ICLC will be administered intramuscularly (IM) twice weekly at one of two dose levels: 1 mg or 2 mg

Each dose level will enroll 3-6 participants, up to 12 participants total, depending on the occurrence of dose limiting toxicities (DLT) at each dosing level.

Participants may receive treatment for 1 year (~17 cycles).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: DRUG

200mg pembrolizumab will be given intravenously on Day 1 of each 3-week cycle

Poly-ICLC

Intervention Type: DRUG

The maximum tolerated dose of Poly ICLC will be given twice weekly, in each 3-week cycle:

Week 1, Days 1 and 4

Week 2, Days 8 and 11

Week 3, Days 15 and 18

Phase 2

In Phase 2, all participants will receive the standard pembrolizumab dose (200 mg IV q3w) in addition to the maximum tolerated dose of poly-ICLC (either 1 mg or 2 mg), as determined by the Phase 1 arm.

Up to 30 participants will be treated in Phase 2. Participants may receive treatment for 1 year (~17 cycles).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: DRUG

200mg pembrolizumab will be given intravenously on Day 1 of each 3-week cycle

Poly-ICLC

Intervention Type: DRUG

The maximum tolerated dose of Poly ICLC will be given twice weekly, in each 3-week cycle:

Week 1, Days 1 and 4

Week 2, Days 8 and 11

Week 3, Days 15 and 18

Interventions

pembrolizumab

200mg pembrolizumab will be given intravenously on Day 1 of each 3-week cycle

Intervention Type: DRUG

Poly-ICLC

The maximum tolerated dose of Poly ICLC will be given twice weekly, in each 3-week cycle:

Week 1, Days 1 and 4

Week 2, Days 8 and 11

Week 3, Days 15 and 18

Intervention Type: DRUG

Other Intervention Names

MK-3475; Keytruda; polyinosinic-polycytidylic acid-polylysine-carboxymethylcellulose; Hiltonol

Eligibility Criteria

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial
• Have measurable disease based on RECIST 1.1 (Phase 2)
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion
• Have a performance status of 0 or 1 on the ECOG Performance Scale
• Have adequate organ function, according to screening labs performed within 10 days of treatment initiation
• Subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication

Exclusion Criteria

• Currently participating/previously participated in a therapeutic study and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years

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

Sponsors

Oncovir, Inc.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Asha Nayak

OTHER

Sponsor Role: lead

Responsible Party

Asha Nayak

Director, Inpatient Oncology Service

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Asha Nayak, MD

Role: PRINCIPAL_INVESTIGATOR

Georgia Cancer Center at Augusta University

Sharad Ghamande, MD

Role: STUDY_DIRECTOR

Georgia Cancer Center at Augusta University

Locations

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

GCC-16047

Identifier Type: -

Identifier Source: org_study_id