Trial of a Personalized and Adaptive Neoantigen Dose-Adjusted Vaccine Concurrently With Pembrolizumab (PANDA-VAC)
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|ClinicalTrials.gov Identifier: NCT04266730|
Recruitment Status : Not yet recruiting
First Posted : February 12, 2020
Last Update Posted : July 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Lung Cancer Squamous Non-small Cell Lung Cancer Squamous Cell Carcinoma of Head and Neck||Biological: PANDA-VAC Drug: Pembrolizumab||Phase 1|
Subjects will be offered clinical trial participation if per RECIST 1.1 they are determined to have stable disease, mixed response, oligoprogressive state (defined as disease progression at a limited number of anatomic sites, with continued response or stable disease at other sites) or non-threatening progressive disease (defined as progression that fits a clinical pattern where the treating physician believes that PD-1 therapy post-progression is appropriate (e.g. multiple sub-centimeter nodules that do not compromise the bronchus)) to an anti-PD-1 or anti-PD-L1 therapy. Eligible subjects will initiate or continue pembrolizumab monotherapy and will have archival tissue and a buccal swab sample (matched normal sample genomic DNA) collected. Whole exome and single cell sequencing studies will be performed using the archival tumor and matched normal sample to identify tumor specific mutations and predict personalized human leukocyte antigen (HLA) binding proteins. Based on this information, 6 neoantigens will be selected for inclusion in the primary personalized vaccine. The primary therapeutic neoantigen vaccine product (PANDA-VAC) will be comprised of 6 peptides at a dose of 300 micrograms (µg) per peptide admixed with local adjuvant Poly-ICLC. PANDA-VAC will be administered subcutaneously to six subjects after their first protocol-mandated disease assessment on pembrolizumab monotherapy. The subjects will receive five priming doses and two booster vaccinations of PANDA-VAC in combination with continued pembrolizumab treatment. Enrollment of the first 3 subjects to receive PANDA-VAC will be staggered by 4 weeks to monitor for acute and subacute adverse events. Subjects with partial response, stable disease, mixed response, oligoprogressive state or non-threatening progressive disease (in the opinion of the treating physician) following the full series of vaccinations may receive adapted vaccine adjusted to address neoantigens emerging during initial PANDA-VAC and pembrolizumab combination therapy. Subjects will have tissue collected for DNA and RNA sequencing and prediction of HLA binding proteins, as delineated above for the initial vaccine production. The therapeutic neoantigen vaccine product will be comprised of up to 2 additional peptides at a dose of 300 μg per peptide (up to 8 total peptides). Peptides targeting neoantigens no longer represented in sequencing data may no longer be included in the neoantigen vaccine product. The primary endpoint of this trial aims to evaluate the safety of the vaccination administered concurrently with pembrolizumab therapy, by estimating the unacceptable toxicity rate.
As generation of either the primary therapeutic or adapted neoantigen vaccine requires: (1) whole exome sequencing studies of the tumor and a matched normal sample from a buccal swab pre-treatment; (2) RNA sequencing of the tumor pre-treatment; and (3) whole exome sequencing of circulating cell-free DNA and DNA derived from circulating tumor cells, information gained from these analyses will also provide extensive exploratory data. With this data, we will study relationships of mutational and genes expression profiles with depth of response to therapy. The purpose of these studies is to generate initial data that will allow us to estimate effect size and variance of the change in immune features with therapeutic neoantigen vaccine treatment in order to design prospective correlative studies in future trials.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of a Personalized and Adaptive Neoantigen Dose-Adjusted Vaccine Administered Concurrently With Pembrolizumab|
|Estimated Study Start Date :||December 1, 2021|
|Estimated Primary Completion Date :||October 1, 2022|
|Estimated Study Completion Date :||October 1, 2032|
Experimental: PANDA-VAC combined with pembrolizumab
The final primary therapeutic neoantigen vaccine product will comprise 6 peptides at a dose of 300 μg per peptide and Poly-ICLC at a dose of 500 μg formulated in an aqueous solution containing <5% DMSO in isotonic dextrose for a total volume of 750 μL. The vaccine will be administered subcutaneously via 3 equal volume (250 μL) injections, one in an arm and one in each leg. The product will be administered on the following schedule: Days 1 and 4 of Week 1, Day 1 of Week 2, Day 1 of Week 3, Day 1 of Week 4, Day 1 of Week 11, and Day 1 of Week 21.
The primary therapeutic neoantigen vaccine product, Personalized and Adaptive Neoantigen Dose-Adjusted Vaccine (PANDA-VAC), will be comprised of 6 peptides at a dose of 300 micrograms (µg) per peptide admixed with local adjuvant Stabilized polyriboinosinic/polyribocytidylic acid (Poly-ICLC).
Other Name: Personalized and adaptive neoantigen dose-adjusted vaccine
Pembrolizumab will be administered at 200 mg IV dose every three weeks. The subject may transition to 400 mg every six weeks if, after the first scan done after start of treatment, they have a partial response or better or after two scans with stable disease or better.
- Number of adverse events in participants as a measure of safety of personalized and dose adjusted antitumor peptide vaccine (PANDA-VAC) administered concomitantly with pembrolizumab. [ Time Frame: 8 weeks ]Safety will be assessed by events occurring after initial treatment for subjects with advanced squamous non-small cell lung cancer, and head and neck squamous cell carcinoma. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Response rate in subjects with advanced squamous non-small cell lung cancer, and head and neck squamous cell carcinoma treated with PANDA-VAC and pembrolizumab [ Time Frame: 2 years ]Response rate will be measured by RECIST 1.1 and iRECIST. Complete response rate (CRR) will also be reported. In the case of treatments beyond progression, the Response Rate 2 (RR2) will be reported.
- Overall survival of subjects with advanced squamous non-small cell lung cancer, and head and neck squamous cell carcinoma treated with PANDA-VAC and pembrolizumab [ Time Frame: 10 years ]Overall survival will be calculated starting from day 1 of PANDA-VAC and pembrolizumab therapy until death from any cause
- Progression-free survival of subjects with advanced squamous non-small cell lung cancer, and head and neck squamous cell carcinoma treated with PANDA-VAC and pembrolizumab [ Time Frame: 10 years ]Progression-free survival (PFS) is defined as the time from day 1 of PANDA-VAC and pembrolizumab until evidence of disease progression per iRECIST (see Appendix C). In the case of treatment beyond progression, PFS1 and PFS2 (defined as the time from progression until next progression) will be reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04266730
|Contact: Catherine Chengfirstname.lastname@example.org|
|Contact: Spencer Laingemail@example.com|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||Jared Weiss, MD||UNC Chapel Hill|