Presentation Number: LBA18_PR. Lecture Time: 09:15-09:27. Speakers: Heinz-Josef J. Lenz (Los Angeles, US) Background

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Terence Lewis
5 years ago
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1 LBA18_PR - Durable Clinical Benefit With Nivolumab (NIVO) Plus Low-Dose Ipilimumab (IPI) as First-Line Therapy in Microsatellite Instability-High/Mismatch Repair Deficient (MSI-H/dMMR) Metastatic Colorectal Cancer (mcrc) Presentation Number: LBA18_PR Lecture Time: 09:15-09:27 Speakers: Heinz-Josef J. Lenz (Los Angeles, US) Background In previously chemotherapy-treated patients with MSI-H/dMMR mcrc from the phase II CheckMate- 142 trial, NIVO + low-dose IPI (1 mg/kg) provided durable clinical benefit (investigator-assessed [INV] objective response rate [ORR] 55%, median duration of response [DOR] not reached, 12-month overall survival [OS] rate 85%) and manageable safety. Here we report the first results of the efficacy and safety of NIVO + low-dose IPI as a first-line (1L) therapy for patients with MSI-H/dMMR mcrc from CheckMate-142. Methods Patients with no prior treatment for MSI-H/dMMR mcrc were treated with NIVO 3 mg/kg every 2 weeks (Q2W) + low-dose IPI every 6 weeks (Q6W) until disease progression. The primary endpoint was ORR (INV; RECIST v1.1). Results Of 45 patients, 51% were male and median age was 66 years. Median follow-up (time from first dose to data cut-off) was 13.8 months (range 9 19). The ORR and disease control rate (DCR) were 60% and 84%, respectively, with a 7% complete response rate (Table). Median DOR was not reached. At 12 months, progression-free survival (PFS) and OS rates were 77% and 83%, respectively. Grade 3 4 treatment-related adverse events (TRAEs) occurred in 16% of patients and 7% of patients had any grade TRAEs leading to discontinuation. Any grade select immune-mediated TRAEs affecting the hepatic (13%), gastrointestinal (11%), pulmonary (2%), and renal (2%) systems resolved in 100% of patients, while those affecting the skin (33%) and endocrine (24%) systems resolved in 45% and 60% of patients, respectively. Conclusions NIVO (Q2W) + low-dose IPI (Q6W) demonstrated robust and durable clinical benefit and was welltolerated as a 1L treatment for MSI-H/dMMR mcrc. These results suggest that NIVO + low-dose IPI may represent a new treatment option for these patients.

2 Table. Efficacy and Safety NIVO + IPI (N = 45) ORR a, n (%) (95% CI) Best overall response, n (%) CR PR SD PD Not determined DCR b, n (%) (95% CI) Median time to response, months (range) Median DOR, months (95% CI) Median PFS, months (95% CI) 12-month rate, % (95% CI) Median OS, months (95% CI) 12-month rate, % (95% CI) TRAEs, n (%) Any grade Grade 3 4 TRAEs leading to discontinuation, n (%) Any grade Grade (60) (44 74) 3 (7) 24 (53) 11 (24) 6 (13) 1 (2) 38 (84) (71 94) 2.6 ( ) NR (11.5 NE) NR (14.1 NE) 77 ( ) NR (NE) 83 ( ) 35 (78) 7 (16) 3 (7) 1 (2)

3 a Patients with CR or PR divided by the number of treated patients b Patients with a CR, PR, or SD for 12 weeks divided by the number of treated patients CI = confidence interval; CR = complete response; NE = not estimable; NR = not reached; PD = progressive disease; PR = partial response; SD = stable disease Clinical trial identification: NCT Editorial Acknowledgement Professional medical writing assistance and editorial assistance was provided by Tanmayi Mankame, PhD, and Christine Craig of PAREXEL International, funded by Bristol-Myers Squibb.

4 LBA19 - Fluoropyrimidine (FP) + bevacizumab (BEV) + atezolizumab vs FP/BEV in BRAFwt metastatic colorectal cancer (mcrc): Findings from Cohort 2 of MODUL a multicentre, randomized trial of biomarker-driven maintenance treatment following first-line induction therapy Presentation Number: LBA19 Lecture Time: 09:27-09:39 Speakers: Axel Grothey (Germantown, US) Background In patients (pts) with mcrc, molecular screening approaches and new biomarkers are required to fully characterize tumours and identify those likely to benefit. The MODUL study (ClinicalTrials.gov: NCT ) is highly adaptable, Phase II signal seeking, and evaluates the theory of tumoural heterogeneity under induction chemotherapy via switch maintenance treatment in first-line mcrc. Methods MODUL follows an umbrella design; pts with measurable, unresectable, previously untreated mcrc receive 16 weeks of induction treatment with FOLFOX + BEV followed by maintenance randomized to either control (FP/BEV) or experimental treatment in one of four cohorts. Here we report results of Cohort 2 (BRAF wt : FP/BEV + atezolizumab). Primary efficacy endpoint: progression-free survival (PFS, per investigator). Secondary endpoints: overall survival (OS); best overall response rate (ORR); disease control rate (DCR); time to treatment response (TTR); duration of response (DoR); ECOG performance status (PS); safety. Results 824 pts were screened, 696 of whom were enrolled to receive induction treatment. 445 pts with BRAF wt mcrc were randomized to maintenance treatment in Cohort 2 (297 pts FP/BEV + atezolizumab; 148 pts FP/BEV). In the primary analysis of Cohort 2 (median follow-up 10.5 months), PFS was not met (HR=0.92; 95% CI ; p=0.48) and OS was immature. ORR, DCR, TTP and DoR showed small numerical differences in favour of experimental treatment. Subgroup treatment interactions were observed for gender, ECOG PS, response at end of induction and initial diagnosis (synchronous vs metachronous disease). In the updated analysis (median follow-up 18.7 months), PFS outcome was unchanged (HR=0.96; 95% CI ; p=0.727) and OS with 51% of pts with an event was HR=0.86; 95% CI ; p=0.28. The safety profiles observed are consistent with previous findings with no new safety signals identified. Conclusions Adding atezolizumab to FP/BEV (standard of care) as first-line maintenance treatment for pts with BRAF wt mcrc did not lead to improvement in efficacy outcomes. Clinical trial identification: ClinicalTrials.gov: NCT Editorial Acknowledgement Editorial assistance was provided by Lee Miller (Miller Medical Communications).

5 Invited Discussant: LBA18_PR and LBA19 Lecture Time: 09:39-09:54 Speakers: Julien Taieb (Paris, FR)

MEETING SUMMARY ESMO 2018, Munich, Germany. Dr. Jenny Seligmann University of Leeds, UK HIGHLIGHTS ON COLORECTAL CANCER

MEETING SUMMARY ESMO 2018, Munich, Germany Dr. Jenny Seligmann University of Leeds, UK HIGHLIGHTS ON COLORECTAL CANCER DISCLAIMER Please note: The views expressed within this presentation are the personal