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
5655 - Bioactivation of napabucasin triggers reactive oxygen species–mediated cancer cell death
Presenter: Fieke Froeling
Session: Poster Display session 3
Resources:
Abstract
4097 - Targeting NRG1-fusions in multiple tumour types: Afatinib as a novel potential treatment option
Presenter: Stephen V Liu
Session: Poster Display session 3
Resources:
Abstract
1129 - Aspirin and Ticagrelor for the prevention of tumour cell induced platelet aggregation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
4514 - Pharmacokinetic/ pharmacodynamic (PK/PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
Presenter: Michele Maio
Session: Poster Display session 3
Resources:
Abstract
5169 - In vitro functional interrogation of viable Circulating Tumor Associated Cells (C-TACs) for evaluating Platin resistance.
Presenter: Stefan Schuster
Session: Poster Display session 3
Resources:
Abstract
5827 - Targeting ARG2 as a novel therapeutic approach for cancer
Presenter: Marcin Grzybowski
Session: Poster Display session 3
Resources:
Abstract
3129 - MPS1 and PLK1 as new therapy targets in TP53 mutated solid tumors
Presenter: Balazs Gyorffy
Session: Poster Display session 3
Resources:
Abstract
2129 - The Tumor Static Exposure (TSE) concept & utility: application to combination treatment of radiation and radiosensitizing agent in tumor xenograft experiments
Presenter: Samer El Bawab
Session: Poster Display session 3
Resources:
Abstract
1814 - General Methodology to Optimize Tumor Treating Fields Delivery Utilizing Numerical Simulations
Presenter: Noa Urman
Session: Poster Display session 3
Resources:
Abstract
3010 - The Australian Exceptional Responders Program: a National collaboration
Presenter: Megan Barnet
Session: Poster Display session 3
Resources:
Abstract