638P - Final results of IMPACT 2, a randomized study evaluating molecular profiling and targeted agents in metastatic cancer at MD Anderson Cancer Center

Background

The primary endpoint of IMPACT2 was to compare the progression-free survival (PFS) between patients treated with matched targeted therapy (MTT) selected on the basis of tumor molecular alterations and those whose treatment was not selected on the basis of alteration analysis (non-targeted therapy, NTT). We report the final results of randomized patients and results of patients who had molecular profiling and were treated with MTT or NTT without consideration for randomization.

Methods

Patients with metastatic cancer and targetable alterations were randomized between the 2 arms (Part A, 5/2014-4/2017, FMI; Part B, 3/2019-9/2023, Tempus). In Part B, patients who declined randomization selected the treatment arm. Cases were presented at Molecular Tumor Board. Of the remaining patients, many were treated without randomization (NCT02152254). PFS was analyzed by treatment type (FDA-approved + investigational (INV), INV alone, or FDA approved/off-label).

Results

Overall, 829 patients with various tumor types (Part A, n= 391; Part B, n=438) were enrolled (med age, 59.5 yrs, range, 18-84; women, 50%; med. No. of prior therapies, 3; most common cancer, GI 34%, head/neck 13.5%, gynecologic 10%, sarcoma 9.53%;most common genomic alterations RAS, 38%; PI3K/AKT/mTOR pathway, 31%). Overall, 109 patients (Group 1) were randomized (Part A) to NTT or MTT or selected their treatment arm (Part B, NTT or MTT). In addition, 297 patients (Group 2) were treated with NTT or MTT without consideration for randomization. Results are shown in the first part of the table. The second part of the table shows the median PFS in months by treatment type (FDA-approved + INV, INV alone, or FDA approved/off-label). Table: 638P

Conclusions

No differences in response, PFS (primary endpoint), or OS was noted between the 2 randomized arms. INV therapy was associated with a shorter PFS than FDA-approved +INV combinations or FDA-approved/off label therapy in most patient subgroups.

Clinical trial identification

NCT02152254.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Foundation Medicine, Tempus, Mr. and Mrs. Steven Mckenzie's Endowment, Katherine Russell Dixie’s Distinguished Professorship Endowment, and donor funds from Jamie's Hope and Mrs. and Mr. James Ritter for Dr. Tsimberidou's Personalized Medicine Program. This work was in part also supported by the National Institutes of Health/National Cancer Institute award number P30 CA016672 (University of Texas MD Anderson Cancer Center).

Disclosure

A.M. Tsimberidou: Financial Interests, Institutional, Funding, No Financial Interest: OBI Pharma; Financial Interests, Institutional, Funding, No financial interest: Agenus, IMMATICS, Tachyon, Novocure, Orionis, Tempus, Tvardi; Financial Interests, Institutional, Funding, No financial interest: Parker Institute for Cancer Immunotherapy; Financial Interests, Personal, Other, Advisory Role: Avstera Therapeutics, Bioeclipse, BrYet, Diaccurate, Macrogenics, NEX-I, VinceRx. S. Fu: Financial Interests, Institutional, Research Grant, Partial grant funding supporting facilities necessary for clinical trials: NIH/NCI P30CA016672 - Core Grant (CCSG Shared Resources); Financial Interests, Institutional, Local PI: Abbisko, Antengene, BeiGene, Ltd, BeyondSpring Phamaceuticals, Inc., BioAtla, Llc., Boehringer Ingelheim, CUE Biopharma, Inc., DEKA Biosciences, Eli Lilly & Co., Exelixis, Greenfire Bio, Inc., Hookipa Biotech, ImmavRx, Inc. (IMV), Innovent Biologics, Co., Ltd., Jazz Pharmaceuticals, K-Group Beta, Lantern Pharma Inc., Lyvgen Biopharm, Co., Ltd., MacroGenics, MediLink Therapeutics, Co. Ltd., Millennium Pharmaceuticals, Inc., Nerviano Medical Sciences, NeuPharma, Inc., NextCure, Inc., Ningbo NewBay Technology Development Co., Ltd., Novartis, NovoCure, Nykode Therapeutics, Parexel International, Llc, PharmaMar USA, Inc., Pionyr Immunotherapeutics, Inc., PureTech Health, Llc, Qurgen, Inc., Sellas Life Sciences Group, Shanghai Huaota Biopharmaceutical Co., Ltd., Soricimed Biopharma, Inc., SQZ Biotechnologies, Sumitomo Dainippon, Taiho Oncology and NCCN, Treadwell Therapeutics, Turnstone Biologics, Tyligand Bioscience, Ltd., Virogin Biotech, Ltd. D.S. Hong: Financial Interests, Personal, Other, Travel, accommodations, expenses: AACR, ASCO, Bayer, Genmab, Gilead, SITC, Telperian; Financial Interests, Personal, Other, Consulting, Speaker, or Advisory Role: AbbVie, Adaptimmune, Alpha Insights, Acuta, Alkermes, Amgen, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, COR2ed, COG, Cowen, Ecor1, Gennao Bio, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, Immunogen, Infinity, Janssen, Liberium, MedaCorp, Medscape, Numab, Oncologia Brasil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, RAIN, SeaGen, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point Therapeutics, WebMD, YingLing Pharma, Ziopharm; Financial Interests, Personal, Advisory Board: 28Bio, Affini-T, Astellas, Fate Therapeutics, CARSgen, InduPro, Projects in Knowledge, Quanta, Ridgeline, Stanford; Financial Interests, Personal, Ownership Interest, Advisor: Molecular Match; Financial Interests, Personal, Ownership Interest, Founder, Advisor: OncoResponse, Telperian; Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Adlai-Nortye, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Erasca, F. Hoffmann-LaRoche, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa Kirin, Loxo, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, TCR2, Teckro, Turning Point Therapeutics, VM Oncology, Biomea, Immunogenesis, Revolution Medicine, STCube. S.A. Piha-Paul: Financial Interests, Personal and Institutional, Funding, support/grant: AbbVie Inc., ABM Therapeutics Inc., Acepodia Inc., Alkermes, Aminex Therapeutics, Amphivena Therapeutics Inc., BioMarin Pharmaceutical Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma Inc., Chugai Pharmaceutical Company Ltd., Curis Inc., Cyclacel Pharmaceuticals, Daiichi Sankyo, Eli Lilly & Company, ENB Therapeutics, Epigenetix Inc., Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Gene Quantum, Genmab A/S, Gilead Sciences Inc., GSK, Helix BioPharma Corporation, Hengrui Pharmaceuticals Company Ltd., HiberCell Inc., Immorna Biotherapeutics Inc., Immunomedics Inc., Incyte Corporation, Jacobio Pharmaceuticals Company Ltd., Jiangsu Simcere Pharmaceutical Company Ltd., Lytix Biopharma ASPuma Biotechnology Inc., Medimmune Llc, Medivation Inc., Merck Sharp and Dohme Corporation, Nectin Therapeutics Ltd., Novartis Pharmaceuticals, Pieris Pharmaceuticals Inc., Pfizer, Phanes Therapeutics, Principia Biopharma Inc., Puma Biotechnology Inc., Purinomia Biotech Inc., Rapt Therapeutics Inc., Replimune, Seattle Genetics, Silverback Therapeutics, Synlogic Therapeutics, Taiho Oncology, Tesaro Inc., TransThera Bio, ZielBio Inc. A. Naing: Financial Interests, Personal, Advisory Board: CTI, Deka Biosciences, Janssen Biotech, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec Keynote 695, Genome & Company, CytomX Therapeutics, Nouscom, Merck Sharp & Dohme Crop, Servier, Lynx Health, AbbVie, PsiOxus; Financial Interests, Institutional, Invited Speaker: AKH Inc., ASCO Direct Oncology Highlights, European Society for Medical Oncology; Financial Interests, Personal, Invited Speaker: Lynx Group, Society for Immunotherapy of Cancer, Korean Society of Medical Oncology, Scripps Cancer Care Symposium, CME Outfitters; Financial Interests, Institutional, Coordinating PI: NCI, EMD Serono; Financial Interests, Personal, Local PI: MedImmune, Healios Onc. Nutrition, Atterocor/Millendo; Financial Interests, Institutional, Local PI: Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab PsiOxus, Arcus Biosciences, NeoImmuneTech, Immune-Onc Therapeutics, Surface Oncology, Monopteros Therapeutics, BioNTech Se, Seven & Eight Biopharma, Sotio Biotech AG; Other, Travel and Accommodation: ARMO BioSciences, NeoImmune Tech; Other, Travel and accommodation: NGM BioPharmaceuticals. J. Rodon: Financial Interests, Personal, Advisory Board: Ellipses Pharma, Ionctura SA, Aadi Bioscience, Envision Pharma, Molecular Partners, Mekanistic, Amgen; Financial Interests, Personal, Other, Consultancy: Clarion Healthcare, Debiopharm, Cullgen, Pfizer, Macrogenics, Oncology One, Columbus Venture Partners, Sardona Therapeutics, Avoro Capital Advisors, Vall d'Hebron Institute of Oncology/Ministero De Empleo Y Seguridad, Chinese University of Hong Kong, Boxer Capital, Llc, Tang Advisors, Llc, Alnylam Pharmaceuticals, Bridgebio Pharma; Financial Interests, Personal, Other, Consultancy/Advisory Board: Monte Rosa Therapeutics, Merus N.V., Incyte; Financial Interests, Institutional, Other, Clinical Research: Novartis, Spectrum Pharmaceuticals, Symphogen, BioAtla, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GSK; Financial Interests, Institutional, Other, Research Funding: Blueprint Medicines, Black Diamond, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Research Funding/Clinical Research: Hummingbird, Yingli; Financial Interests, Institutional, Research Grant, Research Funding: Vall d'Hebron Institute of Oncology/Cancer Core Europe; Financial Interests, Institutional, Research Grant, Clinical Research: Bicycle Therapeutics, Taiho, Roche Pharmaceuticals, Merus, Curis, AadiBioscience, Nuvation, ForeBio, BioMed Valley Discoveries, Loxo Oncology, Cellestia, Deciphera, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics, Bayer, Hutchinson MediPharma; Other: VHIO/Ministero De Empleo Y Seguridad Social; Other, Travel: European Society for Medical Oncology, Loxo Oncology. T.A. Yap: Financial Interests, Personal, Other, Consultant: Almac, Aduro, AstraZeneca, Atrin, Axiom, Bayer, Bristol Myers Squibb, Clovis, Cybrexa, EMD Serono, Guidepoint, Ignyta, I-Mab, Jansen, Merck, Pfizer, Repare, Roche, Schrodinger, Varian, Zai Labs, AbbVie, Acrivon, Adagene, Amphista, Artios, Athena, Avoro, Baptist Health Systems, BeiGene, Boxer, C4 Therapeutics, Calithera, Cancer Research UK, Diffusion, F-Star, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Idience, ImmuneSensor, Institut Gustave Roussy, Intellisphere, Kyn, MEI Pharma, Mereo, Natera, Nexys, Novocure, OHSU, OncoSec, Ono Pharma, Pegascy, PER, Piper-Sandler, Prolynx, resTORbio, Theragnostics, Versant, Vibliome, Xinthera, ZielBio, Radiopharm Theranostics, Sanofi, Ellipses.Life, LRG1, Panangium, Pliant Therapeutics, Synthis, Tessellate Bio, TD2 Theragonostics, Tome Biosciences, Zentalis, Amgen Inc., Astex, Avenzo, BioCity Pharma, Blueprint, Carrick Therapeutics, Circle Pharma, Daiichi Sankyo, Dark Blue Therapeuticcs, Duke Street Bio, 858 Therapeutics, EcoR1 Capital, Entos, FoRx Therapeutics AG, Genesis Therapeutics, Ideaya Biosciences, Impact Therapeutics, Merit, Monte Rosa Therapeutics, Nested Therapeutics, Nimbus, Odyssey, Onxeo, Protai Bio, Ryvu Therapeutics, SAKK, Servier, Synnovation, Tango, TCG Crossover, Terremoto Biosciences, Terns Pharmaceuticals, Tolremo, Tome, Thryv Therapeutics, Trevarx Biomedical, Veeva, Voronoi Inc.; Financial Interests, Personal, Other, University of Texas MD Anderson Cancer Center, where I am Medical Director of the Institute for Applied Cancer Science, which has a commercial interest in DDR and other inhibitors (IACS30380/ART0380 was licensed to Artios): MD Anderson Cancer Center, Institute for Applied Cancer Sciences; Financial Interests, Personal, Stocks/Shares: Seagen; Financial Interests, Institutional, Other, Grant/Research support: Bayer, Cyteir, EMD Serono, GSK, Karyopharm, Pfizer, Repare, Sanofi, Artios, AstraZeneca, BeiGene, BioNTech, Blueprint, BMS, Clovis, Constellation, Eli Lilly, Forbius, F-Star, Genentech, Haihe, ImmuneSensor, Ionis, Ipsen, Jounce, KSQ, Kyowa, Merck, Mirati, Novartis, Ribon Therapeutics, Regeneron, Rubius, Scholar Rock, Seattle Genetics, Tesaro, Vivace, Acrivon, Zenith; Financial Interests, Institutional, Research Grant: Boundless Bio, Ideaya; Financial Interests, Institutional, Other, Grant/Research Support: Insilico Medicine, Tango. D. Karp: Financial Interests, Personal, Advisory Role, Consulting: Black Beret Life Sciences; Financial Interests, Personal, Advisory Role: Affigen; Financial Interests, Personal, Advisory Board, Research and Travel Support: Phosplatin; Financial Interests, Institutional, Funding, Grant: NIH. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd, Amgen, Aileron Therapeutics, Compugen Ltd, Gilead, Bolt Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: BOLT Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics. J.V. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co., Janssen Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK, Spectrum; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Institutional, Other, International PI for clinical trials: AstraZeneca; Financial Interests, Institutional, Other, International PI for two clinical trials: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Institutional, Coordinating PI: Takeda. J.A. Ajani: Financial Interests, Personal, Advisory Board: BMS, Gilead, Astellas, AZ, Jazz, KirinKyowa, Servier, BeiGene, Daiichi; Financial Interests, Institutional, Coordinating PI, My institution receives funding: BMS; Financial Interests, Institutional, Coordinating PI: Merck, Jazz, Astellas, DeltaFly, Gilead, Roche. C. Cartwright, J. BecK: Non-Financial Interests, Institutional, Full or part-time Employment: MD Anderson Cancer Center. D. Vining: Financial Interests, Personal, Member of Board of Directors, founder of a startup company: VisionSR; Financial Interests, Personal, Ownership Interest, founder of a startup company: VisionSR; Financial Interests, Personal, Royalties, I receive royalties for virtual colonoscopy-related products: Bracco Diagnostics. J.S. Ross: Financial Interests, Personal, Full or part-time Employment, Medical Director: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holdings, Tango Therapeutics, Celsius Therapeutics. C. Chao: Financial Interests, Personal, Leadership Role, Sr Vice President, Medical Affairs: Tempus Labs, Inc; Financial Interests, Personal, Stocks/Shares: Tempus Labs, Inc. Chicago, IL. D.A. Berry: Financial Interests, Personal, Ownership Interest: Berry Consultants, Llc. F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, OnCusp Therapeutics, Zymeworks; Financial Interests, Personal, Other, Consulting: Calibr, Ecor1, Exelixis, GT Aperion, Infinity Pharmaceuticals, Loxo Oncology, LegoChem Bio, Lengo Therapeutics, Tallac Therapeutics, Becton Dickinson, eFfector Therapeutics, Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Incyte, Karyopharm, Protai, TheraTechnologies, Zentalis, FogPharma, Harbinger Health, Mersana Therapeutics, Sanofi Pharmaceuticals; Financial Interests, Personal, Other, Consulting: Menarini Group; Financial Interests, Personal, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Invited Speaker: Dava Oncology; Financial Interests, Institutional, Other, Local PI/Research Grant: Aileron Therapeutics, Bayer Healthcare, CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., eFfector Therapeutics, Taiho Pharmaceutical Co.; Financial Interests, Institutional, Other, Local PI/Research/Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Calithera Biosciences, Curis Inc., Debiopharm International, Guardant Health Inc., Klus Pharma, Novartis, Jazz Pharmaceuticals, Zymeworks; Financial Interests, Institutional, Other, Local PI/Steering Committee Member: Genentech Inc.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Co., Puma Biotechnology Inc., Repare; Other, Travel support: European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO); Other, Travel Support: Cholangiocarcinoma Foundation, Dava Oncology. All other authors have declared no conflicts of interest.