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Poster Discussion session - Developmental therapeutics / investigational immunotherapy

4362 - NCI-MATCH Arms N & P: phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Date

20 Oct 2018

Session

Poster Discussion session - Developmental therapeutics / investigational immunotherapy

Topics

Clinical Research;  Translational Research

Tumour Site

Presenters

Filip Janku

Citation

Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279

Authors

F. Janku1, O. Jegede2, S.L. Puhalla3, P. Konstantinopoulos4, F. Meric-Bernstam1, E.P. Mitchell5, J.A. Zwiebel6, L.M. McShane6, S. Li2, L.V. Rubinstein6, L.A. Doyle6, D. Patton7, B.A. Conley6, P.J. O'Dwyer8, L.N. Harris9, C. Arteaga10, P.M. Williams11, S.R. Hamilton12, A.P. Chen13, K.T. Flaherty14

Author affiliations

  • 1 Investigational Cancer Therapeutics, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 2 Ecog-acrin Biostatistics Center, Dana Farber Cancer Institute, 02215 - Boston/US
  • 3 Medical Oncology, The University of Pittsburgh, Pittsburgh/US
  • 4 Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 5 Medical Oncology, Kimmel Cancer Center-Thomas Jefferson University, 19107 - Philadelphia/US
  • 6 Ctep, National Cancer Institute, Bethesda/US
  • 7 Informatics, National Cancer Institute, Bethesda/US
  • 8 Medical Oncology, ECOG-ACRIN, 19104 - Philadelphia/US
  • 9 Cancer Diagnosis Program, National Cancer Institute, Bethesda/US
  • 10 Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas/US
  • 11 Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick/US
  • 12 Pathology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 13 Division Of Cancer Treatment And Diagnosis, Center for Cancer Research-National Cancer Institute, 20892 - Bethesda/US
  • 14 Medical Oncology, Massachusetts General Hospital, 2114 - Boston/US
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Resources

Abstract 4362

Background

The NCI-MATCH trial is the largest national study (1173 sites) for pts with relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns targeted therapies based on individual tumor molecular alterations detected using the adapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC). We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and P may benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.

Methods

Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint.

Results

Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD > 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD > 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm.

Conclusions

Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss.

Clinical trial identification

NCT02465060.

Legal entity responsible for the study

NCI ECOG-ACRIN.

Funding

NCI ECOG-ACRIN.

Editorial Acknowledgement

none

Disclosure

F. Janku: Research support: Bristol-Myers Squibb, Novartis, Genentech, FujiFilm Pharmaceuticals, Plexxikon, Deciphera, Symphogen, Piqur, BioMed Valley Discoveries, and Upsher Smith Laboratories; Scientific Advisory Boards: Deciphera, Guardant Health, IFM Therapeutics; Consultant: Immunomet and Trovagene; Ownership interests: Trovagene. S.L. Puhalla: Consultant: AbbVie, MedImmune, Celldex, Puma, Pfizer, AstraZeneca, Esai, nanostring; Research funding to institution: AbbVie, Pfizer, Lilly, Novartis, Incyte, Covance-Bayer, AstraZeneca, Genentech, Medivation. P. Konstantinopoulos: Advisory boards: Pfizer, Merck and AstraZeneca. P.J. O’Dwyer: Research funding: GSK. All other authors have declared no conflicts of interest.

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