Neoantigen-Targeted Vaccine Combined With Anti-PD-1 Antibody for Patients With Stage IV MMR-p Colon and Pancreatic Ductal Cancer

NCT04799431 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: J2114IRB002704055P50CA062924
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Phase 1 study evaluating feasibility, safety, and immune response to a personalized neoantigen vaccine combined with retifanlimab for MMR-p mCRC and mPDAC patients with measurable disease following first-line FOLFIRINOX/FOLFOXIRI (FFX).

Conditions

Pancreatic Cancer Metastatic; Colorectal Cancer Metastatic

Keywords

Neoantigen Vaccines; Anti-PD-1; Retifanlimab; Cancer Vaccines; Immunotherapy; Colon Cancer; Metastatic colon cancer; Pancreatic Ductal Adenocarcinoma (PDAC); Metastatic pancreatic cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of patients who receive at least one dose of personalized neoantigen vaccine

  Percentage of patients that receive at least one dose of personalized neoantigen vaccine in the maintenance setting among the total number of patients who achieved disease response (eligible for vaccine generation).

  9 months

• Number of participants experiencing study drug-related toxicities

  Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

  2 years

Secondary Outcomes (8)

• Objective Response Rate (ORR) per RECIST 1.1

  2 years

• Objective Response Rate (ORR) per iRECIST

  2 years

• Disease Control Rate (DCR)

  2 months

• Disease Control Rate (DCR)

  6 months

• Disease Control Rate (DCR)

  12 months

Study Arms (1)

Neoantigen Vaccine with Poly-ICLC adjuvant and Retifanlimab

EXPERIMENTAL

All participants receive this intervention.

Drug: Neoantigen Vaccine with Poly-ICLC adjuvant; Drug: Retifanlimab

Interventions

Neoantigen Vaccine with Poly-ICLC adjuvant DRUG

Neoantigen Vaccine with Poly-ICLC adjuvant will be administered on days 1, 8, 15 and 22. 2 to 5 subcutaneous injections will be administered in the upper thighs, arms and/or back. Drug: 0.3 mg per peptide vaccine + 0.5mg Poly-ICLC

Also known as: Hiltonol® (Poly-ICLC)

Neoantigen Vaccine with Poly-ICLC adjuvant and Retifanlimab

Retifanlimab DRUG

500 mg will be administered as a 30 minute IV. Infusion (-5 min/+15min) on Day 1 of each 28 day cycle every 4 weeks.

Also known as: INCMGA00012; MGA012

Neoantigen Vaccine with Poly-ICLC adjuvant and Retifanlimab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Have histologically or cytologically - proven cancer of the pancreas or colon.
• Have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
• Measurable disease as per RECIST 1.1.
• Have sufficient and accessible tissue for NGS and immune-phenotyping.
• Have not received any prior systemic therapy in the metastatic setting for PDA or CRC. Patients who have received adjuvant chemotherapy \>12 months prior to the diagnosis of metastatic disease may be eligible.
• ECOG performance status 0.
• Life expectancy of greater than 6 months.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
• Men must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Is a candidate for definitive surgical resection.
• Is unwilling or unable to undergo standard of care therapy.
• Known history or evidence of brain metastases and/or leptomeningeal spread.
• Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).
• Receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days of vaccine treatment.
• Has active autoimmune disease that has required systemic treatment in the past 5 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
• Known history or concurrent interstitial lung disease.
• Has a pulse oximetry \< 95% on room air.
• Requires the use of home oxygen.
• Infection with HIV or hepatitis B or C.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has been diagnosed with another cancer or myeloproliferative disorder within the past 5 year.
• Has had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
• Has received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.
• If at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Incyte Corporation: collaborator
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Colonic Neoplasms; Pancreatic Neoplasms

Interventions

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; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Nilofer Azad, MD

  SKCCC at the Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 16, 2021
• Study Start: May 3, 2023
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share