Abstract 2553
Background
Treatment options for patients (pts) with BRAFV600 wild type advanced melanoma following failure on anti–programmed death receptor 1 (aPD-1) therapy are limited. Melanoma is strongly driven by MAPK signaling. The MEK inhibitor cobimetinib inhibits MAPK signaling and increases immune cell infiltrate in the tumor, providing a strong rationale for combining cobimetinib with the anti–PD ligand-1 (PD-L1) antibody atezolizumab.
Methods
This multisite, phase Ib study enrolled pts with BRAFV600 wild type advanced melanoma with disease progression on or after aPD-1 therapy (≤12 weeks before study entry) to 2 cohorts. In cohort A, pts received oral cobimetinib 60 mg (once daily, 21 days on, 7 days off) and IV atezolizumab 840 mg (every 2 weeks). In cohort B, pts received identical treatment except in cycle 1, in which cobimetinib was dosed alone for the first 14 days. Paired pretreatment and during-treatment (cycle 2) tumor biopsies were mandated in cohort B. The co-primary endpoints were confirmed objective response rate per RECIST v1.1 and disease control rate (DCR; complete response, partial response [PR], or stable disease [SD] at 16 weeks). Safety was a secondary endpoint (CTCAE v4.0).
Results
At data cutoff (March 1, 2019), 103 pts were enrolled in cohorts A (n = 92) and B (n = 11); 50 pts had >16 weeks of follow-up and were included in this analysis. Of these 50 pts, 8 (16%) had PR as best confirmed response and 18 (36%) had SD; the DCR was 38% (PR = 8; SD at 16 weeks=11). Prior aPD-1 therapy in 9 pts with unconfirmed PR included pembrolizumab (n = 5), nivolumab (n = 1), pembrolizumab + ipilimumab (n = 2), or nivolumab + ipilimumab (n = 1). For the 7 pts with confirmed PR whose tumor PD-L1 status could be established, 6 were positive (≥1% PD-L1+ cells) and 1 was negative (<1% PD-L1+ cells). The most common adverse events were diarrhea (82%), fatigue (58%), dermatitis acneiform (56%), nausea (56%), and vomiting (42%).
Conclusions
Preliminary efficacy and safety data for the combination of cobimetinib and atezolizumab in pts who have disease progression on/after prior aPD-1 therapy suggest that this is a feasible and active option warranting further exploration.
Clinical trial identification
NCT03178851.
Editorial acknowledgement
ApotheCom, Yardley, PA, USA.
Legal entity responsible for the study
Roche.
Funding
Roche.
Disclosure
S.K. Sandhu: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Endocyte. V.G. Atkinson: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Travel / Accommodation / Expenses: Onco-Sec. M. Gonzalez Cao: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Takeda. T. Medina: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array; Research grant / Funding (institution): Dynavax; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Checkmate. A. Soria Rivas: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono. I. Caro: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche Genentech. L. Roberts: Full / Part-time employment: Genentech. Y. Song: Full / Part-time employment: Roche/Genentech. Y. Yan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncosec; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche.
Resources from the same session
4489 - A Window of Opportunity Trial of Atorvastatin Targeting p53 Mutant Malignancies
Presenter: Joaquina Baranda
Session: Poster Display session 3
Resources:
Abstract
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
2661 - Tumor stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumors.
Presenter: Myriam Fabre
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract