Abstract 749P
Background
CheckMate 032 is a multicohort, phase 1/2 trial evaluating N monotherapy (3 mg/kg; N3) and 2 different regimens of N+I (N 3 mg/kg + I 1 mg/kg [N3I1] or N 1 mg/kg + I 3 mg/kg [N1I3]) in pts with platinum-pretreated mUC. Long-term results with a minimum follow-up of 56.2 mo (N3), 57.0 mo (N3I1), and 26.7 mo (N1I3) are reported.
Methods
This multicenter, open-label trial enrolled pts with previously treated advanced or mUC, RECIST v1.1 measurable disease, and ECOG performance status ≤1. Pts received N3 Q2W or either N3I1 or N1I3 Q3W for 4 cycles followed by N3 Q2W until disease progression or unacceptable toxicity. The primary endpoint was investigator (inv)-assessed objective response rate (ORR) per RECIST v1.1 with duration of response (DOR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. ORR and PFS were also assessed by blinded independent central review (BICR).
Results
ORR per inv was 26% (N3), 26% (N3I1), and 42% (N1I3); ORR by BICR was similar (Table). Median DOR per inv was 30.5, 22.3, and 29.7 mo, respectively. ORR benefit by BICR was observed in all cohorts regardless of tumour PD-L1 status but was highest in N1I3 pts with PD-L1 ≥1% (58%). Median PFS per inv was 2.8, 2.6, and 4.9 mo with N3, N3I1, and N1I3, respectively, and was similar by BICR. Median OS was 9.9, 7.4, and 15.3 mo, respectively. Any-grade treatment-related adverse events (TRAEs) occurred in 85% (grade 3–4, 27%), 85% (grade 3–4, 32%), and 80% (grade 3–4, 42%) of pts in N3, N3I1, and N1I3 arms, respectively. One pt each in the N3 and N3I1 arms had a grade 5 TRAE (pneumonitis). Table: 749P
| N3 n = 78 | N3I1 n = 104 | N1I3 n = 92 | |
| Min. study follow-up, mo | 56.2 | 57.0 | 26.7 |
| ORR per inv, % (95% CI) | 26 (16–37) | 26 (18–36) | 42 (32–53) |
| ORR by BICR, % (95% CI) | 22 (13–33) | 23 (15–32) | 38 (28–49) |
| PD-L1 ≥1%a | 23 (9–44) | 32 (17–51) | 58 (39–76) |
| PD-L1 <1%a | 21 (10–36) | 23 (13–36) | 21 (10–37) |
| Median DOR per inv, mo (95% CI) | n = 20 30.5 (8.3–41.6) | n = 27 22.3 (9.8–NE) | n = 39 29.7 (9.3–NE) |
| Median DOR by BICR, mo (95% CI) | n = 17 41.6 (16.4–57.0) | n = 24 NR (20.8–NE) | n = 35 NR (13.8–NE) |
| Median PFS per inv, mo (95% CI) | 2.8 (1.5–5.4) | 2.6 (1.4–3.9) | 4.9 (2.8–6.6) |
| Median PFS by BICR, mo (95% CI) | 2.8 (1.5–3.9) | 2.5 (1.5–3.9) | 4.3 (2.7–8.2) |
| Median OS, mo (95% CI) | 9.9 (7.3–18.6) | 7.4 (5.6–11.0) | 15.3 (8.1–25.6) |
aBy immunohistochemistry NE, not estimable; NR, not reached
Conclusions
With extended follow-up, all arms continue to show meaningful anti-tumour activity and manageable safety profiles. The risk:benefit profile of N1I3 is promising and supports the development of this dosing regimen vs chemotherapy in the ongoing phase 3 CheckMate 901 trial in previously untreated pts with mUC (NCT03036098).
Clinical trial identification
NCT01928394.
Editorial acknowledgement
Professional medical writing and editorial assistance was provided by Jenny Reinhold of Parexel, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
P. Sharma: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Oncolytics; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Patents : Jounce ; Advisory/Consultancy, Shareholder/Stockholder/Stock options: BioAtla; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Forty-Seven; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Polaris; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Marker; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Codiak; Advisory/Consultancy, Shareholder/Stockholder/Stock options: ImaginAB; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Hummingbird ; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Dragonfly; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Lytix; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Lava Therapeutics ; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Achelois; Advisory/Consultancy: Infinity ; Shareholder/Stockholder/Stock options: Constellation; Shareholder/Stockholder/Stock options: Apricity Health; Shareholder/Stockholder/Stock options: Neon. A.O. Siefker-Radtke: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Nektar ; Advisory/Consultancy, Research grant/Funding (institution), grants pending: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: NCCN; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), grants pending: BioClin Therapeutics; Advisory/Consultancy: Bavarian Nordic; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Genentech; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Mirati; Research grant/Funding (self), pending grant: NIH; Research grant/Funding (self), pending grant: Michael and Sherry Sutton Fund for Urothelial Cancer; Research grant/Funding (institution), pending grant: Takeda; Research grant/Funding (institution), pending grant: Merck Sharp & Dohme. F. de Braud: Honoraria (self): Tiziana Life Sciences; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Novartis; Honoraria (self): Servier; Honoraria (self): Pharm Research Associated; Honoraria (self): Daiichi Sankyo; Honoraria (self): Ignyta; Honoraria (self): Amgen; Honoraria (self): Pfizer; Honoraria (self): Octimet Oncology; Honoraria (self): Incyte; Honoraria (self): Teofarma; Honoraria (self): Pierre Fabre; Honoraria (self): Eli Lilly; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Gentili; Honoraria (self): Dephaforum; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Bayer; Honoraria (self): Fondazione Menarini. U. Basso: Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen-Cilag; Advisory/Consultancy: MSD; Advisory/Consultancy: Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (self): Ipsen; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Sanofi. E. Calvo: Advisory/Consultancy, Tahio Grant : Boehringer-Ingelheim; Research grant/Funding (institution), Tesaro Grent : Roche/Genentech; Research grant/Funding (institution), Janssen-Cilag Consultation fees: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Seattle Genetics Consultation fees: Novartis; Advisory/Consultancy, Pierre Fabre Consultation fees: PsiOxus; Advisory/Consultancy, Cerulean Pharma Consultation fees: Nanobiotix Janssen; Advisory/Consultancy, EUSA Consultation fees: Abbvie; Research grant/Funding (institution), Celgene Consultation fees: PharMar; Research grant/Funding (institution), START Employement, Ownership, Leadership: PUMA; Research grant/Funding (institution), HM Hospital Group Employment, honoraria: Sanofi; Research grant/Funding (institution), Oncoart Associated Ownership: Lilly; Research grant/Funding (institution), International Cancer Consultants Ownership: Pfizer; Research grant/Funding (institution), NPO Foundation Intheos President and Founder: Merck; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Amcure; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Principia Bayer; Research grant/Funding (institution): CytomX; Research grant/Funding (institution): H3; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Kura; Research grant/Funding (institution): LOXO; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Menarini; Research grant/Funding (institution): Merck.Serono; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Rigontec; Research grant/Funding (institution): Tahio. P. Bono: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Orion Pharma; Honoraria (self): Ipsen; Honoraria (self), Shareholder/Stockholder/Stock options: Faron Pharmaceutical; Honoraria (self): Oncorena; Shareholder/Stockholder/Stock options: TILT Bio therapeutics. M. Morse: Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Speaker Bureau/Expert testimony: Taiho; Research grant/Funding (institution): AlphaVax; Research grant/Funding (institution): Halozyme; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: Genetech; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Chugai; Advisory/Consultancy, Research grant/Funding (institution): Ipsen. P.A. Ascierto: Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Roche-Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (self): Array; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Incyte; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: Medimmune; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi Advisory/Consultancy: Idera; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Immunocore; Advisory/Consultancy: 4SC; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco; Advisory/Consultancy: Nektar; Advisory/Consultancy: Boehringer-Ingelheim. J. Lopez-Martin: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Pfizer-Merck/Serono; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: MSD ; Honoraria (self), Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony, Shareholder/Stockholder/Stock options: Pharmamar; Advisory/Consultancy: Chobani. P. Brossart: Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Amgen; Honoraria (self): Roche; Honoraria (self): GSK; Honoraria (self): AbbVie; Honoraria (self): AstraZeneca. K.S. Rohrberg: Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Research grant/Funding (self): Loxo Oncology; Research grant/Funding (self): Bayer; Research grant/Funding (self): Orion Pharma; Research grant/Funding (self): Pfizer; Research grant/Funding (self): PUMA; Research grant/Funding (self): Cantargia; Research grant/Funding (self): Genmab; Research grant/Funding (self): Novartis; Research grant/Funding (self): Incyte; Research grant/Funding (self): Symphogen; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Alligator; Research grant/Funding (self): Merck; Research grant/Funding (self): Pierre Fabre. B. Mellado: Honoraria (self), Research grant/Funding (self): Astellas; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Jansen; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self), Research grant/Funding (self): Sanofi; Honoraria (self), Research grant/Funding (self): Roche; Non-remunerated activity/ies: BMS; Honoraria (self): Merck; Honoraria (self), Non-remunerated activity/ies: Pfizer. S. Li: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. C. Baudelet: Full/Part-time employment: Bristol Myers Squibb. K. Unsal-Kacmaz: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. M.K. Callahan: Research grant/Funding (institution), Spouse/Financial dependant: Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Moderna. J.E. Rosenberg: Research grant/Funding (institution): Novartis; Advisory/Consultancy: Astellas; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Bayer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Mirati Therapeutics; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: EMD-Serono; Advisory/Consultancy: Adicet Bio; Advisory/Consultancy: Western Oncolytics; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy: Sensei Biotherapeutics; Advisory/Consultancy: BioClin Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): QED Therapeutics; Advisory/Consultancy: Fortress Biotech; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Stock sold 2019: Merck; Honoraria (self): Chugai; Shareholder/Stockholder/Stock options, Stock sold 2019: Illumina; Advisory/Consultancy: GSK; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Janssen.