Abstract 553P
Background
NCI-MATCH assigned patients (pts) with advanced cancer and progression on prior treatment to targeted therapies, based on genomic alterations in pre-treatment tumour tissue. Arm J evaluated the combination of trastuzumab/pertuzumab (HP) across HER-2 amplified tumours.
Methods
Eligible pts had HER2 amplification (copy number [CN] ≥7) detected by central next generation sequencing (NGS) or through NCI designated laboratories. Pts with breast/gastroesophageal adenocarcinoma, and those who received prior HER2-directed therapy, were excluded. Enrolment of pts with colorectal cancer was capped at 4 based on emerging data. Pts received HP IV Q3 weeks until disease progression or unacceptable toxicity, with restaging q3 cycles. Primary endpoint was objective response (ORR); enrolment of 35 pts provided 92% power to distinguish an ORR of 25% from a null of 5%, with one-sided type 1 error of 1.8%. Secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Data cut was 8-FEB-2020.
Results
35 pts were enrolled 3/2017-6/2019; 2 were ineligible. Tumour types included gynecologic (n=14), hepatobiliary (10), colorectal (4), urothelial (3), esophageal squamous, and salivary gland (1 each). 58% were women, and 79% Caucasian. Median age was 64 (range 31-83), and 51% had ≥3 prior therapies (range 1- 11). Median cycles received was 3 (1-20). Of 33 treated, 24 had CN ≥7 confirmed by central lab (median CN=28). The confirmed ORR was 8.3% (2/24 partial responses [colorectal and cholangiocarcinoma], 90% CI 1.5-24%). There was one additional unconfirmed partial response (PR, urothelial cancer). Median PFS was 3.3 months (90% CI 2.0 - 4.6), 6-month PFS 23.3% (90% CI 13.6 – 40.1) and median OS 8.1 months (90% CI 5.5 - 12.4). Treatment-emergent adverse events were consistent with prior HP studies. There was no association between HER2 CN and response.
Conclusions
HP had activity in a minority of tumours in this population, but did not meet the predefined efficacy benchmark for non-breast/gastroesophageal cancers with HER2 amplifications by NGS. Translational studies will focus on mechanisms of response and resistance.
Clinical trial identification
NCT02465060.
Editorial acknowledgement
Legal entity responsible for the study
ECOG-ACRIN.
Funding
ECOG-ACRIN, NCI, Genentech.
Disclosure
R.M. Connolly: Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Marcogenics. D.M. Hyman: Shareholder/Stockholder/Stock options: Lilly/Loxo; Full/Part-time employment: Lilly/Loxo. P. Grivas: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Biocept; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Driver; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Genzyme; Advisory/Consultancy: Heron Therapeutics; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: Mirati Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Oncogenex; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Debiopharm. E. Mitchell: Advisory/Consultancy: Genentech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck; Research grant/Funding (institution): Genentech. C.L. Arteaga: Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Radius; Advisory/Consultancy: TAIHO Oncology; Advisory/Consultancy: PUMA Biotechnology; Advisory/Consultancy: Merck; Advisory/Consultancy: H3 Biomedicine; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: OrigiMed; Advisory/Consultancy: Petra Pharma; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Athenex; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Clovis; Advisory/Consultancy: AbbVie; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Bayer; Shareholder/Stockholder/Stock options: Provista; Shareholder/Stockholder/Stock options: Y-TRAP; Officer/Board of Directors: Scientific Advisory Board Susan G Komen Breast Cancer Foundation; Officer/Board of Directors: American Association of Cancer Institutes. P.J. O'Dwyer: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): BMS; Research grant/Funding (institution): GSK; Research grant/Funding (institution): FivePrime; Research grant/Funding (institution): FortySeven; Research grant/Funding (institution): BBI; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Lilly/Imclone; Research grant/Funding (institution): Array; Research grant/Funding (institution): H3Biomedicine; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Pharmacyclics/Abbvie; Advisory/Consultancy: Genentech; Advisory/Consultancy: Array; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: Lilly. K.T. Flaherty: Officer/Board of Directors: Clovis Oncology; Officer/Board of Directors: Strata Oncology; Officer/Board of Directors: Vivid Biosciences; Officer/Board of Directors: Checkmate Pharmaceuticals; Advisory/Consultancy: X4 Pharmaceuticals; Advisory/Consultancy: PIC Therapeutics; Advisory/Consultancy, Also received Research funding from Sanofi. ESMO site doesn't allow room to enter. : Sanofi; Advisory/Consultancy: Amgen; Advisory/Consultancy: Asana; Advisory/Consultancy: Adaptimmune; Advisory/Consultancy: Fount; Advisory/Consultancy: Aeglea; Advisory/Consultancy: Shattuck Labs; Advisory/Consultancy: Tolero; Advisory/Consultancy: Apricity; Advisory/Consultancy: Oncoceutics; Advisory/Consultancy: Fog Pharma; Advisory/Consultancy: Neon Tvardi; Advisory/Consultancy: X Cures; Advisory/Consultancy: Monopteros; Advisory/Consultancy: Vibliome; Advisory/Consultancy: Lilly; Advisory/Consultancy, Also received Research funding from Novartis. ESMO site doesn't allow room to enter. : Novartis; Advisory/Consultancy: Genentech; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: Takeda; Advisory/Consultancy: Verastem; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.