GEM and Nab-P is a standard first line therapy for mPDAC based on the MPACT Trial. D is a human monoclonal antibody (mAb) that inhibits binding PD-L1 to its receptor. T is a mAb directed against CTLA-4. PA.7 is designed to evaluate whether combining PD-L1 and CTLA-4 inhibition with GEM and Nab-P increases treatment efficacy.
This randomized phase II study (NCT02879318) assessed the efficacy and safety of GEM, Nab-P, D, and T (arm A) vs GEM and Nab-P (arm B) in patients (pts) with mPDAC (n=191). Pts with untreated mPDAC and good performance status (ECOG PS 0-1) were eligible. A safety run in was conducted for 11 pts receiving GEM, Nab-P, D and T. The study then randomized 180 pts in a 2:1 ratio to receive GEM (1000mg/m2 D1, 8, 15); Nab-P (125mg/m2 D1, 8, 15); D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles vs. GEM and Nab-P alone. The primary endpoint is overall survival (OS); secondary endpoints include progression free survival (PFS), safety, overall response rate (ORR) and quality of life.
180 pts were randomized (119 to arm A and 61 to arm B) between April 2017 and July 2018. Baseline characteristics were well balanced. With a median (med) follow-up of 28.5 months (mo) there was no significant difference in OS (med 9.8 mo in arm A vs. 8.8 mo in arm B, Hazard Ratio (HR)=0.94, 90% confidence interval (CI) 0.71-1.25, p=0.72). There was no significant difference in PFS (med 5.5 mo vs 5.4 mo respectively, HR=0.98, 90% CI 0.75-1.29, p=0.91). ORR was not significantly different, 30.3% vs. 23.0% respectively (Odds Ratio=1.49, 90% CI 0.81-2.72, p=0.28). Disease control rate (DCR) was 70.6% vs 57.4% respectively (difference=13.2%, 90% CI 0.7-25.7%, p=0.096). The only significant difference in grade 3 or greater adverse events was lymphopenia (38% vs 20% respectively, p=0.02).
The addition of dual immune checkpoint inhibitors to Gem and Nab-P did not result in a significant improvement in OS, PFS, or ORR. There is a trend to improved DCR. Correlative analyses to assess biomarkers that may predict immune sensitivity in this setting are underway.
Clinical trial identification
Legal entity responsible for the study
Canadian Cancer Trials Group.
D.J. Renouf: Advisory/Consultancy: Celgene; Advisory/Consultancy: Servier; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Taiho; Advisory/Consultancy: Bayer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. J.J. Knox: Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Merck; Research grant/Funding (self): Ipsen; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Eisai. M. Tehfe: Honoraria (institution), Research grant/Funding (self): Celgene; Honoraria (self), Advisory/Consultancy: AstraZeneca. N. Aucoin: Advisory/Consultancy: Celgene; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer. R. Ramjeesingh: Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self): Astrazeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: Servier. All other authors have declared no conflicts of interest.