Abstract 572P
Background
Despite approvals of immune checkpoint inhibitors (ICI), there is still a subset of histologies classified as “cold” with objective response rates (ORR) <10% and no drug approvals. We assessed the benefit of anti-PD1/L1 combinations in early clinical trials in patients (pts) with advanced cold tumors.
Methods
From 2015 to 2019, 70 pts were treated with anti-PD1/L1-based combination strategies in early clinical trials at VHIO (excluding pts pre-exposed to ICI). Clinico-pathological data and anti-tumour activity were extracted from a prospective database. ORR was defined as per RECIST v1.1 criteria and clinical benefit rate (CBR) as complete/partial response (CR/PR) + stable disease (SD) for ≥ 4 months (m). Kaplan Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated and a Cox model according to LIPI (Lung Immune Prognostic Index = baseline LDH and derived neutrophil to lymphocyte ratio) was constructed.
Results
In the overall population, 53% were male, median age was 60y, 57% had ECOG 0, 88% received ≥2 prior treatment lines, 57% had liver metastases and 20% had LIPI good prognostic score. Most pts had microsatellite stable (MSS) colorectal cancer (57%), ovarian cancer (11%) and adrenal carcinoma (7%). Regimens included anti-PD1/L1 + another ICI in 87% (most commonly anti-LAG3 [28.5%], CD40 agonist [20%], A2AR inhibitor [13%]), anti-PD1/L1 + anti-VEGFR or anti-TGFβ in 7% and bispecific antibodies (anti-PD1/L1 + anti-LAG3 or CD137 agonist) in 6%. ORR was 1.42% (mesothelioma treated with anti-PD1 + anti-LAG3). CBR was 14.28% (6 pts with MSS colorectal, 2 ovarian and 2 mesothelioma), all treated with ICI doublets. Median PFS for overall and CBR populations were 1.9 m (CI95% 1.8-2.0) and 4.2 m (3.9-NA), respectively. Median OS for overall population was 7.4 m (6.2-9.9), with a trend for improved OS if LIPI good score vs. others (9.5 m vs. 6.8 m, hazard ratio 1.93, 95% CI (0.75-4.95), p=0.16).
Conclusions
In our cohort, anti-PD1/L1-based combination strategies demonstrated limited activity in pts with unselected cold tumours. Further drug-biomarker co-development strategies are needed to increase chances of response.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
O. Saavedra Santa Gadea: Honoraria (self): Kyowa Kirin; Travel/Accommodation/Expenses: MSD. A. Hernando-Calvo: Honoraria (self): Kyowa Kirin. I. Matos: Research grant/Funding (self): Roche. A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Pharma; Advisory/Consultancy: Amcure GmbH. M. Vieito Villar: Advisory/Consultancy: DEBIO; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Merck Serono. I. Braña: Advisory/Consultancy: Orion Pharma; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy: Rakutan Pharma; Speaker Bureau/Expert testimony: Roche. G. Argiles Martinez: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Hoffman La-Roche; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: Menarini; Honoraria (institution): Novartis; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Boston Pharmaceuticals; Honoraria (institution): Genentech. T. Macarulla Mercadé: Honoraria (self), Advisory/Consultancy: Advance Medical HCMS ; Honoraria (self), Advisory/Consultancy: Batxer; Honoraria (self), Advisory/Consultancy: BioLineRX Ltd; Honoraria (self), Advisory/Consultancy: Celgene SLU; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: IPSEN Pharma lab; Honoraria (self), Advisory/Consultancy: Menarini; Honoraria (self), Advisory/Consultancy: Lab. Servier; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: QED Therapeutics; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Prime Oncology EU; Honoraria (self), Advisory/Consultancy: Sanofi-Aventis; Honoraria (institution): Agios; Honoraria (institution): Aslan; Honoraria (institution): AstraZeneca; Honoraria (institution): Bayer; Honoraria (institution): Celgene; Honoraria (institution): Genentech; Honoraria (institution): Hallozyme; Honoraria (institution): Immunomedics; Honoraria (institution): Merimarck; Honoraria (institution): Millenim; Honoraria (institution): Novartis; Honoraria (institution): Pfizer ; Honoraria (institution): Pharmacyclics; Honoraria (institution): Roche. J. Capdevila: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Exelixis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Advanced Accelerator Applications; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono. S. Cedres: Advisory/Consultancy: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: F.Hoffmann La Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy: MSD Oncology. A. Oaknin: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: ImmunoGen; Honoraria (self), Advisory/Consultancy: Genmab. E. Elez: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Hoffman La Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Sanofi Aventis; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Honoraria (institution), Advisory/Consultancy: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Array Pharmaceuticals; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Bristol- Myers Squibb; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): AbbVie; Honoraria (institution): Pierre-Fabre; Honoraria (institution): Novartis; Honoraria (institution): GlaxoSmithKline; Honoraria (institution): Medimmune. J. Tabernero: Honoraria (self), Advisory/Consultancy: Array Biopharma; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: BeiGene; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Chugai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Genmab ; Honoraria (self), Advisory/Consultancy: Halozyme; Honoraria (self), Advisory/Consultancy: Imugene Limited ; Honoraria (self), Advisory/Consultancy: Inflection Biosciences Ltd; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Kura Oncology; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Menarini; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: Merrimack; Honoraria (self), Advisory/Consultancy: Merus; Honoraria (self), Advisory/Consultancy: Molecular Partners; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Peptomyc; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Pharmacyclics ; Honoraria (self), Advisory/Consultancy: ProteoDesign SL; Honoraria (self), Advisory/Consultancy: Rafael Pharmaceuticals ; Honoraria (self), Advisory/Consultancy: F. Hoffmann-La Roche Ltd; Honoraria (self), Advisory/Consultancy: SeaGen; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Servier. R. Dienstmann: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Speaker Bureau/Expert testimony: Ipsen; Honoraria (self), Speaker Bureau/Expert testimony: Amgen; Honoraria (self), Speaker Bureau/Expert testimony: Servier; Honoraria (self), Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck; Research grant/Funding (self): Pierre Fabre. E. Garralda: Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Thermo Fisher; Advisory/Consultancy: Genentech; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Neomed Therapeutics1 INC; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: SeaGen; Advisory/Consultancy: TFS; Advisory/Consultancy: Alkermes; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Mayers Squibb; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Menarini; Travel/Accommodation/Expenses: Glycotope. All other authors have declared no conflicts of interest.