Pembrolizumab + Poly-ICLC in MRP Colon Cancer

NCT02834052 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: GCC-16047
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colon Cancer; Solid Tumor

Keywords

Immunotherapy; Anti-programmed death 1 (PD-1) inhibitor; Immunostimulant; monoclonal antibody; TLR3 agonist; Immunologic factors

Outcome Measures

Primary Outcomes (3)

• Phase 1: Determine the Maximum Tolerated Dose of Poly-ICLC That Can be Combined With Pembrolizumab

  A minimum of 3 participants will be treated at dose level 1 (1mg). * If 0 out of 3 participants experience dose limiting toxicities (DLT), then dose escalation will proceed to dose level 2 (2mg). * If 1 out of 3 participants experience DLT, a cohort of additional 3 participants will be assigned to the same dose level (1mg). * If 2 or more participants of 3 (or 6) experience DLT at dose level 1, then enrollment of participants will be stopped.

  12 months

• Phase 1 and 2: Determine the Response Rate of Metastatic MRP Colon Cancer (That Has Progressed Following Two Lines of Therapy in the Metastatic Setting) to the Combination of Pembrolizumab and Poly-ICLC

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  From baseline to disease progression (Expected 12-24 months)

• Determine the Overall Survival Rate for Recurrent Metastatic MRP Colon Cancer Response to the Combination of Pembrolizumab and Poly-ICLC

  The overall survival rate of response to the combination of pembrolizumab and poly-ICLC administered at the Recommended Phase 2 Dose (RP2D) will be estimated along with the correspondent 95% confidence interval.

  From baseline to disease progression (up to 24 months)

Secondary Outcomes (3)

• Determine the Adverse Event Profile and Dose Limiting Toxicities of the Combination of Pembrolizumab and Poly-ICLC

  12 months

• Determine the 20-week Progression Free Survival Rate of Recurrent Metastatic MRP Colon Cancer to the Combination of Pembrolizumab and Poly-ICLC

  20 weeks

• Determine the Duration of Response of Recurrent Metastatic MRP Colon Cancer to the Combination of Pembrolizumab and Poly-ICLC

  From baseline to disease progression (up to 24 months)

Study Arms (2)

Phase 1

EXPERIMENTAL

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).

Drug: pembrolizumab; Drug: Poly-ICLC

Phase 2

EXPERIMENTAL

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).

Drug: pembrolizumab; Drug: Poly-ICLC

Interventions

pembrolizumab DRUG

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

Also known as: MK-3475, Keytruda

Phase 1; Phase 2

Poly-ICLC 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

Also known as: polyinosinic-polycytidylic acid-polylysine-carboxymethylcellulose, Hiltonol

Phase 1; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asha Nayak: lead
• Oncovir, Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; poly ICLC

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Dr Asha Nayak
• Organization: AUGUSTA UNIVERSITY MEDICAL CENTER

anayak@augusta.edu

7067216748

Study Officials

• Asha Nayak, MD

  Georgia Cancer Center at Augusta University

  PRINCIPAL INVESTIGATOR

• Sharad Ghamande, MD

  Georgia Cancer Center at Augusta University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Inpatient Oncology Service

Study Record Dates

• First Submitted: June 15, 2016
• First Posted: July 15, 2016
• Study Start: January 10, 2018
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: June 7, 2024
• Results First Posted: June 7, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)