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Proffered Paper – Melanoma and other skin tumours

2804 - Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: primary analysis from the phase 3 IMspire170 trial

Date

28 Sep 2019

Session

Proffered Paper – Melanoma and other skin tumours

Presenters

Ana Arance

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

A.M. Arance1, H. Gogas2, B. Dreno3, K.T. Flaherty4, L. Demidov5, D. Stroyakovskiy6, Z. Eroglu7, P.F. Ferrucci8, J. Pigozzo9, P. Rutkowski10, J. Mackiewicz11, I. Rooney12, A. Voulgari13, S. Troutman12, B. Pitcher14, Y. Yan15, J.M.G. Larkin16

Author affiliations

  • 1 Medical Oncology, Hospital Clínic Barcelona, 08036 - Barcelona/ES
  • 2 School Of Medicine, University of Athens, 115 27 - Athens/GR
  • 3 Department Of Dermatology, CHU Nantes, 44093 - Nantes/FR
  • 4 Hematology/oncology, Massachusetts General Hospital, Harvard Medical School, 02114 - Boston/US
  • 5 Melanoma Unit, Department Of General Surgery, Russian Oncological Research Centers, 115478 - Moscow/RU
  • 6 Chemotherapy, Moscow City Oncology Hospital No. 62, 143423 - Moscow/RU
  • 7 Department Of Cutaneous Oncology, H. Lee Moffitt Cancer Center, 33612 - Tampa/US
  • 8 Unit Of Oncology Of Melanoma, European Institute of Oncology, 20141 - Milan/IT
  • 9 Department Of Cutaneous Oncology, Melanoma Oncology Unit, Veneto Institute of Oncology IOV – IRCCS, 35128 - Padua/IT
  • 10 Department Of Soft Tissue/bone Sarcoma, The Maria Sklodowska Curie Memorial Cancer Centre and Institute of Oncology (MCMCC), 02-781 - Warsaw/PL
  • 11 Oddział Onkologii Klinicznej I Doświadczalnej, Uniwersytet Medyczny w Poznaniu, 61-866 - Poznań/PL
  • 12 Product Development, Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 13 Global Product Development Clinical Science, Roche Products Ltd, AL7 1TW - Welwyn Garden City/GB
  • 14 Product Development, Oncology, Hoffmann-La Roche Ltd., L5N 5M8 - Mississauga/CA
  • 15 Oncology Biomarker Development, Genentech, Inc., South San Francisco/US
  • 16 Department Of Medicine, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
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Abstract 2804

Background

Treatment for pts with advanced BRAFV600 wt melanoma includes immune checkpoint inhibitors, such as P, an anti–PD-1 antibody. MAPK activation is implicated in BRAFV600 wt melanoma, and emerging data suggest that MAPK inhibition may enhance antitumor immune response to checkpoint inhibitors. In a phase I study, the combination of C, a MEK inhibitor, plus A, an anti–PD-L1 antibody, showed promising antitumor activity. In a phase III randomized study we evaluated whether C+A would improve efficacy compared with P monotherapy in pts with BRAFV600 wt advanced melanoma.

Methods

Pts had previously untreated unresectable stage III or IV BRAF V600 wt melanoma. Pts were stratified by PD-L1 expression, LDH level, and geographic location, and were randomized 1:1 to receive C (60 mg, days 1-21) plus A (840 mg, every 2 wk) in 28-day cycles or P (200 mg, every 3 wk) until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. Primary endpoint was PFS, assessed by independent review committee (IRC). Key secondary endpoints were confirmed objective response rate (ORR), disease control rate (DCR), OS, and safety.

Results

446 pts were randomized to C+A (n = 222) or P (n = 224); 68% of pts had PD-L1–positive tumors and 25% had LDH >ULN. Median follow-up was 7 mo (range 0-15). C+A did not significantly improve IRC-assessed PFS vs P (median 5.5 vs 5.7 mo; HR 1.15; 95% CI 0.88-1.50; P = 0.295). Results were consistent across pt subgroups. Confirmed IRC-assessed ORR was 26% vs 32% with C+A vs P; DCR was 46% vs 44%. Median OS was not reached in either arm (HR 1.06; 95% CI 0.69-1.61). AEs were consistent with known safety profiles of the individual agents. Grade ≥3 AEs occurred in 67% vs 33% of pts receiving C+A vs P; AEs leading to discontinuation of all treatments occurred in 12% vs 6%.

Conclusions

IMspire170 did not meet its primary endpoint. The combination of C+A did not demonstrate an improvement in PFS vs P monotherapy in pts with BRAFV600 wt advanced melanoma. The safety profile of C+A was consistent with that observed in previous studies of this combination.

Clinical trial identification

NCT03273153.

Editorial acknowledgement

ApotheCom, Yardley, PA, USA.

Legal entity responsible for the study

Roche.

Funding

Roche.

Disclosure

A.M. Arance: Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp and Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck. H. Gogas: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (institution), Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Roche. B. Dreno: Advisory / Consultancy: Roche. K.T. Flaherty: Advisory / Consultancy, Shareholder / Stockholder / Stock options, BMS: advisory/consultancy: X4 Pharmaceuticals; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Merck: advisory/consultancy; research grant (institution): PIC Therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Takeda: advisory/consultancy: Sanofi; Advisory / Consultancy, Verastem: advisory/consultancy: Amgen; Advisory / Consultancy, Boston Biomedical: advisory/consultancy: Asana; Advisory / Consultancy, Pierre Fabre: advisory/consultancy: Adaptimmune; Advisory / Consultancy, Cell Medica: advisory/consultancy: Fount; Advisory / Consultancy, Debiopharm: advisory/consultancy; research grant (institution): Aeglea; Advisory / Consultancy, Research grant / Funding (institution), Clovis Oncology: shareholder/stock: Array BioPharma; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Strata Oncology: shareholder/stock: Shattuck Labs; Advisory / Consultancy, Vivid Biosciences: shareholder/stock: Tolero; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Checkmate Pharmaceuticals: shareholder/stock: Apricity; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Oncoceutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Fog Pharma; Advisory / Consultancy: Neon; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tvardi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: xCures; Advisory / Consultancy: Monopteros; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Genentech. L. Demidov: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BIOCAD; Research grant / Funding (self): Amgen. D. Stroyakovskiy: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis. Z. Eroglu: Advisory / Consultancy: Array; Advisory / Consultancy: Regeneron; Research grant / Funding (institution): Novartis. P.F. Ferrucci: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis. J. Pigozzo: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. P. Rutkowski: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Travel / Accommodation / Expenses: Orphan Drugs. J. Mackiewicz: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. I. Rooney: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. A. Voulgari: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. Troutman: Full / Part-time employment: Genentech. B. Pitcher: Full / Part-time employment: Roche. Y. Yan: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech. J.M.G. Larkin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Vitaccess: honoraria (self)/advisory/consultancy/travel: Achilles; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Covance: research grant (institution): AZ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Immunocore: research grant (institution): Boston Biomedical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Pharmacyclics: research grant (institution): BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Aveo: research grant (institution): Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EUSA Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: GSK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Imugene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: iOnctura; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Kymab; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Secarna.

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