Abstract 573P
Background
Despite positive effects of ICIs in multiple tumor types, lack of harmonized biomarkers remains a challenge. In clinical practice, efficacy to prior ICIs remains a key determinant when considering patient (pts) enrollment into novel IT trials. We investigated whether benefit with prior ICIs impacts on outcomes for subsequent IT.
Methods
Pts treated with IT trials at VHIO Phase 1 Unit from 2016-2019 were reviewed. Among 568, 101 pts with prior ICI exposure were selected. Clinico-pathological and laboratory data were collected at baseline prior to phase 1 IT trial (IT-Phase1) initiation. Kaplan Meier estimates of progression-free survival (PFS) and objective response rate (ORR) by RECIST 1.1 were calculated for the IT-Phase1 and for the prior IT line (IT-priorPhase1). 3 cohorts were defined depending on IT-priorPhase1 best response (BR): Refractory (Refr) as those with progression as BR, Rechallenge (Rech) as those achieving a partial response (PR) to IT-priorPhase1 and having progressed to another therapy between IT treatments; and Rescue (Resc) for any other case.
Results
Out of 101 pts, median age was 58y, all ECOG ≤1, treated with single agent IT-Phase1 16 (16%) or combinations 85 (84%). Median prior lines were 2 (1-7) and median follow-up was 8.1 months (mo). Most common tumors were melanoma 45%, NSCLC 21% and HNSCC 11%. Based on IT-priorPhase1, 48% were categorized as Refr, 20 % Rech and 33% Resc. Overall, ORR was 18% for IT-priorPhase1 and 11% for IT-Phase1, not different according to IT-priorPhase1 category of BR (p= 0.67). Median PFS was 2.4 mo (2 - 3.7) and 2.5 mo (2 - 3.6) for IT-priorPhase1 and IT-Phase1, respectively (p= 0.49). In an unadjusted Cox model, there were no differences in PFS with IT-Phase1 depending on IT-priorPhase1 category of BR (p= 0.60). In a multivariable Cox model with tumor type, number of metastatic sites, ECOG, LIPI score, single vs. combination treatment, and IT-priorPhase1 BR category, the only significant predictor of PFS was metastatic burden (p= 0.01).
Conclusions
In our cohort, BR during IT-priorPhase1 was not associated with treatment outcomes for IT phase I trials. Our results suggest that other prognostic factors should be taken into account when considering early clinical trials with IT for pts having progressed to prior ICIs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vall d’Hebron Institute of Oncology.
Funding
Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI) supported by the Banco Bilbao Vizcaya Argentaria Foundation (BBVA Foundation) (grant 89/2017). La Caixa Foundation (LCF/PR/CEO7/50610001). Cellex Foundation providing research facilities and equipment.
Disclosure
A. Hernando-Calvo: Travel/Accommodation/Expenses: Kyowa Kirin. O. Saavedra Santa Gadea: Travel/Accommodation/Expenses: Kyowa Kirin; Travel/Accommodation/Expenses: MSD. I. Braña: Advisory/Consultancy, Leadership role: Orion Pharma; Speaker Bureau/Expert testimony, Leadership role: BMS; Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Senoro; Advisory/Consultancy, Leadership role: Rakutan Pharma; Speaker Bureau/Expert testimony: Roche; Leadership role: Cellgene; Leadership role: Gliknik; Leadership role: GSK; Leadership role: Janssen; Leadership role: KURA; Leadership role: MSD; Leadership role: Novartis; Leadership role: Pfizer; Leadership role: Shattuck; Leadership role: Northern Biologics; Leadership role: Nanobiotics. I. Matos: Research grant/Funding (self), ESMO Research Fellowship: Roche. M. Vieito: Advisory/Consultancy: Debio; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Merck Senoro. A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Pharma; Advisory/Consultancy, Research grant/Funding (self): Amcure GmbH. H. Verdaguer: Advisory/Consultancy: Ipsen. M. Gonzalez: Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Lilly. I. Baraibar Argota: Honoraria (self): Sanofi; Travel/Accommodation/Expenses: Amgen. A. Callejo: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: F. Hoffmann-La Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy: Kyowa Kirin; Travel/Accommodation/Expenses: Cellgene. E. Munoz Couselo: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi; Honoraria (self): Amgen; Advisory/Consultancy: Bristol-Myers Squibb. J. Tabernero: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BeiGene; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai; Advisory/Consultancy: Genetech; Advisory/Consultancy: Inc.; Advisory/Consultancy: Genmab A/S; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Imugene Limited; Advisory/Consultancy: Inflection Biosciences Limited; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Kura Oncology; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Menarini; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Merus; Advisory/Consultancy: Molecular Partners; Advisory/Consultancy: Novartis; Advisory/Consultancy: Peptomyc; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy: ProteoDesign SL; Advisory/Consultancy: Rafael Pharmaceuticals; Advisory/Consultancy: F.Hoffman-La Roche Ltd; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seagen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, Halio DX SAS and Roche Diagnostics. R. Dienstmann: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Merck Sharp and Dohme; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Pierre Fabre. E. Garralda: Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Thermo Fisher; Advisory/Consultancy: Roche/Genetech; Advisory/Consultancy: F.Hoffmann/La Roche; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Neomed Therapeutics1 Inc; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Janssen Global Services; Advisory/Consultancy: SeaGen; Advisory/Consultancy: TFS; Advisory/Consultancy: Alkermes; Advisory/Consultancy, Speaker Bureau/Expert testimony: Thermo Fisher; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Sharp and Dohme; Travel/Accommodation/Expenses: Menarini; Travel/Accommodation/Expenses: Glycotope. All other authors have declared no conflicts of interest.