Abstract 2613
Background
ICI and VEGFR-targeted therapies are the primary treatments for mRCC. Len plus Eve is currently approved based on improved progression-free survival (PFS) in pts with progressive disease after one prior VEGFR-targeted therapy. However, its efficacy beyond second-line, and after ICI, is not well defined.
Methods
We conducted a retrospective study of pts with mRCC who were treated with Len alone, or in combination with Eve, after at least 2 prior lines of therapy, including ICI and VEGFR-TKI. We report clinical benefit (CB), defined as partial response (PR) + stable disease (SD), PFS, overall survival (OS), and adverse events (AE).
Results
Between 11/2016 and 2/2019, we identified 40 pts with mRCC who were treated with Len +/- Eve. Median age was 59 years (range, 34-76); 62.5% were male; 52.5% had ECOG PS 1 and 35% had ECOG PS 2; 77.5% had clear cell histology; 85% had prior nephrectomy and 95% had metastatic disease in >/= 3 sites; 2.5% had IMDC favorable-risk, 87.5% intermediate-risk, and 10% poor-risk disease. The median number of prior lines of therapy was 4 (range, 2-10); 70% received Len+Eve and 62.5% were treated with Len +/- Eve as 5th-line or later. All pts had prior ICI exposure, primarily nivolumab monotherapy (70%), and 87.5% received >/= 2 prior VEGFR-TKIs. CB was achieved in 67.5% (30% PR + 37.5% SD). At a median follow up of 8.5 months (mo), median PFS was 4.2 mo (95% CI, 3.4-6.5), with a 6-mo PFS probability of 34% (95% CI, 21%-54%). Median OS was 10.8 mo (95% CI, 5.4-13.3), with a 1-year OS probability of 37% (95% CI, 21%-65%). Twenty-three pts (57.5%) have died, and of those only 4 received further therapies after Len +/- Eve. Dose reduction was required in 45% of pts, and the most common grade 3 or 4 AEs were proteinuria (17.5%), fatigue (10%), and diarrhea (10%). Treatment was discontinued in 4 pts (10%) because of toxicity.
Conclusions
Len alone and in combination with Eve demonstrated clinical benefit, with an overall response rate of 30%, and was well tolerated in heavily pretreated pts with mRCC after prior ICI and VEGFR-targeted therapies, supporting its use in this patient population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Z. Lim: Speaker Bureau / Expert testimony: Exelixis. M.T. Campbell: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), non-branded educational programs: EMD Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), non-branded educational programs: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Apricity Health; Research grant / Funding (self): Exelixis; Research grant / Funding (self): Janssen; Speaker Bureau / Expert testimony, non-branded educational programs: Bristol-Meyers Squibb; Speaker Bureau / Expert testimony, non-branded educational programs: Roche; Speaker Bureau / Expert testimony, non-branded educational programs: Merck. A.Y. Shah: Honoraria (self), Research grant / Funding (self): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): EMD Serono. A. Zurita Saavedra: Speaker Bureau / Expert testimony: McKesson Specialty Health; Speaker Bureau / Expert testimony: Janssen-Cilag, S.A.DEC.V.; Advisory / Consultancy: Incyte; Advisory / Consultancy: Pfizer. E. Jonasch: Advisory / Consultancy, Research grant / Funding (self): Exelixis; Advisory / Consultancy, Research grant / Funding (self): Novartis; Research grant / Funding (self): Peloton; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Roche. N.M. Tannir: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Calithera Biosciences Inc.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai Medical Research; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy, Travel / Accommodation / Expenses: Oncorena; Research grant / Funding (self): Epizyme; Research grant / Funding (self): Mirati Therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent
Presenter: Kristin Hicks
Session: Poster Display session 3
Resources:
Abstract
3190 - GI101, a novel triple-targeting bispecific CD80-IgG4-IL2variant fusion protein, elicits synergistic anti-tumor effects in preclinical models
Presenter: Jae Chan Park
Session: Poster Display session 3
Resources:
Abstract
4062 - Phase 1b, open-label, dose-escalation study of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumors
Presenter: Julius Strauss
Session: Poster Display session 3
Resources:
Abstract
5777 - THOR-707, a novel not-alpha IL-2, promotes all key immune system anti-tumoral actions of IL-2 without eliciting vascular leak syndrome (VLS)
Presenter: Marcos Milla
Session: Poster Display session 3
Resources:
Abstract
5047 - A phase I clinical trial of malignant pleural mesothelioma treated with locally delivered autologous anti-FAP-targeted CAR T-cells
Presenter: Alessandra Curioni
Session: Poster Display session 3
Resources:
Abstract
1679 - HPV16 E6-specific TCR-T armored with checkpoint blockade in the treatment of cervical cancer
Presenter: Paul Bryson
Session: Poster Display session 3
Resources:
Abstract
1133 - the Mutant Neoantigen Specific T Cell Is a Personalized Immunotherapy in Refractory Solid Tumor
Presenter: Qi Song
Session: Poster Display session 3
Resources:
Abstract
3338 - NY-ESO-1 and LAGE1A –an emerging target for cell therapies in solid tumours
Presenter: Ioanna Eleftheriadou
Session: Poster Display session 3
Resources:
Abstract
3089 - Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model
Presenter: Mikael Sodergren
Session: Poster Display session 3
Resources:
Abstract
5991 - Master Checkpoint Cbl-b Inhibition: Anti-tumor Efficacy in a Murine Colorectal Cancer Model Following siRNA-based Cell Therapy
Presenter: Kathrin Thell
Session: Poster Display session 3
Resources:
Abstract