NCT05419011

Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

A Phase IIB Clinical Trial of the Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury) Vaccines (TRI-AD5) and IL-15 Superagonist N-803 in Lynch Syndrome

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 186 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase IIb trial tests whether Tri-Ad5 in combination with N-803 works to prevent colon and other cancers in participants with Lynch syndrome. Each of the three injections in Tri-Ad5 vaccine contain a different substance that is in precancer and cancer cells. Injecting these substances may cause the immune system to develop a defense against cancer that recognizes and destroys any precancer and cancer cells that produce these proteins in the future. N-803 may increase immune responses to other vaccines. Giving Tri-Ad5 in combination with immune enhancing N-803 may lower the chance of developing colon and other cancers in participants with Lynch syndrome.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate if the combination of trivalent adenovirus-5 (Tri-Ad5) vaccines and IL-15 superagonist nogapendekin alfa inbakicept (N-803) reduces the incidence of colorectal neoplasms in patients with Lynch syndrome (LS). SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the Tri-Ad5 vaccines + N-803 in combination. II. To correlate clinical factors such as use of aspirin and non-steroidal anti-inflammatory drugs (NSAID), smoking and alcohol intake with immune responses. III. To evaluate the effect of Tri-Ad5 vaccines on the incidence of LS-related extracolonic cancers. IV. To systematically measure the participants' behavior and experience in terms of vaccine uptake, cancer-specific distress and quality of life. EXPLORATORY OBJECTIVES: I. To determine the ability of the Tri-Ad5 vaccines + N-803 to generate a 2-fold increase in T cell responses (cell-mediated immunity) at week 12 (early immune response) and at week 56 (long-term memory response). II. To evaluate circulating anti-MUC1 IgG (antibody-mediated immunity) after Tri-Ad5 vaccines + N-803. III. To compare the expression of the three tumor associated antigen (TAAs): MUC1, carcinoembryonic antigen (CEA) and brachyury in colorectal neoplasms before and after Tri-Ad5 vaccines + N-803. IV. To evaluate changes in the immune profile and abundance of resident immune cell types in colonic mucosa after vaccination with Tri-Ad5 vaccines + N-803 using messenger ribonucleic acid sequencing (mRNAseq) and immunohistochemistry (IHC). V. To test the effects of the vaccines alone or in combination with N-803 on specific immune subsets of peripheral blood mononuclear cells (PBMCs) and serum soluble factors and cytokines. VI. To compare the expression of stem cell markers in colorectal neoplasms before and after Tri-Ad5 vaccines + N-803. VII. To compare the number of mismatch repair deficient (MMR-deficient) crypts at baseline to the number of MMR-deficient crypts at the one year post-vaccination colonoscopy both overall and on a per patient basis. OUTLINE: SAFETY PHASE I: Participants receive Tri-Ad5 subcutaneously (SC) at weeks 0, 4, 8, and 52. Participants also undergo standard of care (SOC) colonoscopy with biopsy at baseline, at 52 weeks and 104 weeks. SAFETY PHASE II: Participants receive Tri-Ad5 SC and N-803 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline, 52 weeks and 104 weeks. RANDOMIZED CONTROL PHASE: Participants are randomized into 1 of two arms. ARM I: Participants receive Tri-Ad5 SC and N-803 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 and 104 weeks. ARM II: Participants receive placebo SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 and 104 weeks. Participants undergo blood sample collection throughout the study.

Conditions

• Colorectal Carcinoma
• Colorectal Neoplasm
• Lynch Syndrome

Interventions

Type	Name	Description
BIOLOGICAL	Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5	Given SC
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Colonoscopy	Undergo SOC colonoscopy
DRUG	Nogapendekin Alfa	Given nogapendekin alfa inbakicept (N-803) SC
DRUG	Placebo Administration	Given SC
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2023-05-08
• Primary completion: 2027-07-01
• Completion: 2028-01-01
• First posted: 2022-06-15
• Last updated: 2026-04-13

Locations

14 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study