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Mini Oral session: Investigational immunotherapy

736MO - Personalized, off-the-shelf KRAS neoantigen-specific immunotherapy for the treatment of advanced solid tumors: Clinical benefit associated with decreases in ctDNA (SLATE-KRAS)

Date

10 Sep 2022

Session

Mini Oral session: Investigational immunotherapy

Topics

Clinical Research;  Targeted Therapy;  Immunotherapy

Tumour Site

Presenters

Chrisann Kyi

Citation

Annals of Oncology (2022) 33 (suppl_7): S331-S355. 10.1016/annonc/annonc1058

Authors

C.K. Kyi1, A. Spira2, D.P. Carbone3, M.L. Johnson4, B.S. Henick5, B. Johnson6, H. Borghaei7, A. Mahipal8, J.R. Hecht9, D. Catenacci10, C. Liao11, A. Shergill11, R. Memmott3, C. Presley3, J. Jaroslavsky12, D. Schenk12, K. Jooss12, A.R. Ferguson12, J.W. Goldman9

Author affiliations

  • 1 Early Drug Development Service, Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2 Research Institute, Virginia Cancer Specialist, 22031 - Fairfax/US
  • 3 Internal Medicine Department, The Ohio State University - OSU Wexner Medical Center, 43210 - Columbus/US
  • 4 Lung Cancer Research, Sarah Cannon Research Institute-Cancer Centre, 37203 - Nashville/US
  • 5 Medicine, Columbia University Medical Center College of Physicians & Surgeons - New York Presbyterian Hospital, 10032 - New York/US
  • 6 Division Of Cancer Medicine, MD Anderson Cancer Center, 77030 - Houston/US
  • 7 Hematology/oncology Department, Fox Chase Cancer Center - Main Campus, 19111-2497 - Philadelphia/US
  • 8 Oncology, Mayo Clinic, 55905 - Rochester/US
  • 9 Medicine, UCLA Hematology/Oncology Santa Monica, 90404 - Santa Monica/US
  • 10 Catenacci Consulting Ltd, Catenacci Consulting Ltd, 60637 - Chicago, IL/US
  • 11 Medicine - Hematology/oncology Section, University of Chicago Department of Medicine - Section of Hematology/Oncology, 60637-1470 - Chicago/US
  • 12 R&d, Gritstone bio, Inc., 94608 - Emeryville/US
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Resources

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Abstract 736MO

Background

Targeting neoantigens derived from common driver mutations with a viral-based prime/boost vaccine can induce strong neoantigen-specific CD8 T cell responses and is a promising off-the-shelf immunotherapy.

Methods

A phase 1/2 study was conducted in patients (pts) with metastatic solid tumors harboring a specific vaccine-targeted neoepitope (HLA class I-restricted). The version 1 (V1) vaccine targeted 20 shared neoantigens from KRAS, TP53, b-catenin, and BRAF. An improved V2 vaccine only targeted KRAS neoantigens (G12C/D/V, Q61H). Pts receive an adenovirus prime followed by boosts with a self-amplifying mRNA with IV nivolumab 480 mg Q4W +/- SC ipilimumab 30 mg with vaccinations. Primary endpoints were safety (Phase 1) and response per RECIST v1.1 (Phase 2).

Results

26 pts with solid tumors were treated with V1. In pts with NSCLC (n=13, post-IO), 1 pt had an unconfirmed partial response (PR), 3 had stable disease (SD; one pt with -18% shrinkage completing 2 years of treatment), and 9 had progressive disease (PD). Molecular response was observed in 3 of 6 ctDNA-evaluable NSCLC pts (defined as > 50% decrease relative to baseline). Analysis of tumors showed increases in IFNg-related genes and vaccine-induced T cells. A V2 vaccine developed to target KRAS neoantigens more effectively induced greater levels of CD8 T cells than V1 in the first pts analyzed. 11 pts have been treated with V2 (NSCLC [n=4, post-IO] and MSS-CRC [n=7]). 1 NSCLC pt had an unconfirmed PR correlating with an 80% decrease in ctDNA. 2 pts with CRC had SD (one ongoing with >85% reduction in ctDNA, CA 19-9, and CEA and -14% shrinkage), and 5 pts with CRC had PD. 3 V2 pts progressed prior to the first boost vaccination at 4 weeks suggesting treating in earlier lines may provide time to generate robust neoantigen-specific CD8 T cells. The most common (>20%) treatment-related adverse events (TRAEs) were low grade, transient pyrexia, fatigue, nausea, injection-site reactions, vomitting, and chills and consistent across V1 and V2.

Conclusions

This off-the-shelf, neoantigen-specific vaccine demonstrated promising anti-tumor activity in pts with advanced solid tumors with tumor regression and/or molecular response.

Clinical trial identification

GO-005, NCT03953235, SLATE-KRAS.

Editorial acknowledgement

Legal entity responsible for the study

Gritstone Bio, Inc.

Funding

Gritstone Bio, Inc.

Disclosure

C.K. Kyi: Financial Interests, Institutional, Principal Investigator: Merus, Gritstone bio, BMS. A. Spira: Financial Interests, Personal, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: Next Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Invited Speaker: LAM Therapeutics, Roche, AstraZeneca, Novartis, Boehringer Ingelheim, Astellas Pharma, MedImmune, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mersana, Mirati Therapeutics, Rubius, Synthekine, Blueprint Medicines. D.P. Carbone: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi-Sar, Eisai, EMD Serono/Merck, Flame Biosciences, Gritstone bio, GSK, Eli Lilly, Sanofi, Seattle Genetics. M.L. Johnson: Financial Interests, Personal, Advisory Board: Astellas, Otsuka; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Amgen, Apexigen, Arcus, Array, AstraZeneca, Atreca, Beigene, Birdie, Boehringer Ingelheim, Checkpoint Therapeutics, Guardant Health, Genocea, Hengrui, Immunocore, Incyte, Janseen, Jounce, Gritstone bio, Lycera, Merck, Mirati, Oncomed, Regeneron, Ribon, Sanofi, Shattuck Labs, Stem CentRx, Syndax, Takeda, Tarveda, TCR2 Therapeutics, University of Michigan, WindMIL. B. Johnson: Financial Interests, Personal, Advisory Board: Gritstone bio, Inc., Incyte, Taiho Oncology; Financial Interests, Personal, Research Grant: BMS, Syntrix. H. Borghaei: Financial Interests, Personal, Advisory Board: BMS, Genentech, Eli-Lilly, Merck, EMD-serono, AstraZeneca, Novartis, Genmab, Regeneron, Amgen, Takeda, PharmaMar, Jazz Pharma, Mirati, Daiichi, Guardant, Natera, Oncocyte, Beigene, iTeo, Boehringer Ingelheim; Financial Interests, Personal, Training Discussion: Pfizer; Financial Interests, Personal, DSMB: Novartis; Financial Interests, Institutional, Clinical trial support: BMS, Amgen; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory role: Sonnetbio; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory board: Nucleai, Inspira (Rgenix); Financial Interests, Institutional, Invited Speaker, Investigator initiated trial support: BMS, Amgen, Lilly; Financial Interests, Personal and Institutional, Invited Speaker, Chair steering committee: Miratti; Financial Interests, Personal and Institutional, Invited Speaker: Amgen, AstraZeneca; DSMB: Novartis, Takeda, Incyte. A. Mahipal: Financial Interests, Personal, Advisory Board: Taiho, Incyte. J.R. Hecht: Financial Interests, Personal, Advisory Board: Ipsen, Merck, Acrotech Biopharma; Financial Interests, Institutional, Research Grant: ARMO Biosciences, Halozyme, Amgen, Merck, AbbVie, Advaxis, Astellas, Forty Seven, Immunomedics, Lilly, Gritstone bio, GSK, Arcus. D. Catenacci: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Bristol Myers Squibb, Five Prime Therapeutics , Genentech/Roche, Gritstone bio, Inc, Guardant Health , Lilly, Merck, Seattle Genetics, Taiho, Tempus; Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine, Genentech/Roche, Guardant Health, Merck, Tempus. C. Liao: Financial Interests, Personal, Advisory Board: AstraZeneca, FirstThought LLC, Transthera, BluePrints Medicine, QED, Genentech, Cancer Experts Now, Histosonics, Ipsen, Exelixis; Financial Interests, Personal, Speaker Bureau: Eisai, Incyte; Financial Interests, Personal, Invited Speaker: OncLive; Financial Interests, Institutional, Invited Speaker, Research funding for investigator initiated trial: BMS. C. Presley: Financial Interests, Personal, Advisory Role: Onc Live, Potentia Metrics. J. Jaroslavsky: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc.. D. Schenk: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc.. K. Jooss: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc.. A.R. Ferguson: Financial Interests, Personal, Full or part-time Employment: Gritstone bio, Inc.. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech, Eli Lilly, Janssen, AbbVie; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Genentech, Eli Lilly, Janssen, BMS, AbbVie. All other authors have declared no conflicts of interest.

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