Interim results from the OPTIMAL trial: A phase II clinical trial of combination nivolumab, ipilimumab, and taxane in patients with untreated metastatic non-small cell lung cancer (NSCLC).

Abstract

e21683 Background: Combination chemo-immunotherapy is a well-established frontline therapeutic option for treatment naïve NSCLC. Dual immune checkpoint blockade (ICB) with nivolumab (nivo) and ipilimumab (ipi) has demonstrated improved clinical outcomes compared with chemotherapy alone in this setting. Combination dual ICB with low-dose chemotherapy may have advantages of preventing early disease progression and potentiating immunogenic response to treatment. Methods: We are conducting a single arm phase II clinical trial of nivo 360 mg IV Q3 weeks, ipi 1 mg/kg IV Q6 weeks, and weekly paclitaxel 80 mg/m2 IV on d1 and d8 of a 21 day cycle in ECOG 0-1 patients (pts) with treatment naïve NSCLC. Paclitaxel is stopped after a total of 4-6 cycles. The primary endpoint of the trial is progression free survival (PFS) with secondary endpoints of safety and objective response rate (ORR) by independent radiologic review. Interim results are presented from the first 23 evaluable pts, of a planned sample size of 49. Results: 23 pts were enrolled and evaluable with a mean age 63.8 years, 56.5% ECOG 0, 87% current/previous smoking history, and 70% adenocarcinoma. PDL1 score for < 1%, 1-49%, ³ 50% was seen in 9 (39.1%), 4 (17.4%), and 10 (43.5%) pts, respectively. Median time of follow up was 6.5 months (range 1.4–15.0). Partial response was observed in 14 pts, stable disease was seen in 8 pts, and 1 pt progressed during cycle 1, resulting in an ORR of 61%. Grade 3 or higher toxicity at least possibly attributed to study treatment was seen in 47.8% of 23 AE evaluable patients, of which included 4 cases of secondary adrenal insufficiency. Other toxicity rates were as expected for the respective agents. Conclusions: This is the first trial to evaluate weekly paclitaxel with nivo plus ipi in pts with untreated NSCLC. This regimen has demonstrated highly encouraging clinical activity with a manageable toxicity profile. The study is ongoing and updated results will be presented at the annual meeting. Clinical trial information: NCT03573947.