Nataliya Trunova

P1.46: Phase I Study of Nivolumab + Nab-Paclitaxel in Solid Tumors: Preliminary Analysis of the Non-Small Cell Lung Cancer Cohort: Track: Advanced NSCLC

by 10 mg decrements to a minimum of 20 mg/day. The incidence and severity of common AEs before and after dose reduction were analyzed, and PK data collected during the standard visit schedules on Days 22 and 43 was compared in patients who reduced to 30 mg versus those remaining at 40 mg/day. PFS in patients who dose reduced within the first 6 months of treatment was compared with those who remained on 40 mg/day. Results: Dose reductions occurred in 53% (122/229) of patients in LL3 and 28% (67/239) of patients in LL6. The majority (LL3: 86%; LL6: 82%) of dose reductions occurred within the first 6 months of treatment. Dose reduction led to decreases in incidence and severity of EGFR-mediated drug-related AEs across LL3 and LL6 (Table). A combined PK analysis of LL3 and LL6 suggested that dose reduction was more likely in patients with higher afatinib plasma concentrations. Patients who dose reduced to 30 mg had geometric mean plasma afatinib concentrations of 45.6 ng/mL on Day 22 (n1⁄422) and 23.3 ng/mL on Day 43 (n1⁄459), compared with those who remained on 40 mg with concentrations of 24.3 ng/ mL on Day 22 (n1⁄4282) and 22.8 ng/mL on Day 43 (n1⁄4284). Across LL3 and LL6, median PFS was similar in patients who dose reduced during the first 6 months of treatment versus those who remained on 40 mg/day (LL3: 11.3 vs 11.0 months, HR1⁄41.25 [95% CI: 0.91e1.72]; LL6: 12.3 vs 11.0 months, HR1⁄41.00 [95% CI: 0.69e1.46]). Conclusion: In LL3 and LL6, afatinib demonstrated a trend towards improved overall survival (OS) versus chemotherapy in the overall study populations and significant OS improvements in patients with EGFR Del19positive disease. Results from this post-hoc analysis indicate that tolerability-guided dose adjustment of afatinib reduces treatment-related AEs without adversely affecting efficacy.

nab-paclitaxel/carboplatin induction in squamous NSCLC: Longitudinal quality of life while on chemotherapy

Background Longitudinal data on the impact of treatment on quality of life (QoL) in advanced non-small cell lung cancer (NSCLC) are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ≤4 cycles of nab-paclitaxel/carboplatin combination chemotherapy. Methods Patients received nab-paclitaxel 100 mg/m2 days 1, 8, 15 + carboplatin area under the curve 6 mg•min/mL day 1 (q3w) for four cycles. QoL was assessed by the Lung Cancer Symptom Scale (LCSS) and Euro-QoL-5 Dimensions-5 Levels (EQ-5D-5L) at baseline and each cycle (day 1). Results Two-hundred and six lesion-response-evaluable patients completed baseline + ≥1 postbaseline QoL assessment and were QoL evaluable. LCSS average total score and symptom burden index improved from baseline throughout four cycles. In the LCSS pulmonary symptoms score, 46% of patients reported clinically meaningful improvement (≥10 mm visual analog scale) from baseline. Individual EQ-5D-5L dimensions remained stable/improved in ≥83% of patients; ≈33% reported complete resolution of baseline problems at least once during four cycles. Generally, responders (unconfirmed complete/partial response) had higher scores vs nonresponders. Conclusion In patients with squamous NSCLC, four cycles of nab-paclitaxel/carboplatin demonstrated clinically meaningful QoL improvements, with greater benefits in responders vs nonresponders.

P1.47: ABOUND.sqm QoL by Response: Interim Analysis of Squamous NSCLC Pts Treated With nab-Paclitaxel/Carboplatin Induction Therapy: Track: Advanced NSCLC.

Method: The primary objective of part 1 is to evaluate dose-limiting toxicities (DLTs). Patients (pts) treated with 2 cycles of nivo with chemotherapy (CT) and remained on study for 14 additional calendar days or who discontinued due to DLT prior to completing 2 cycles of nivo were considered DLT evaluable. Treatment arms could expanded in Part 2 to further assess safety, tolerability, and antitumor activity. The lung arms, C and D, were initiated sequentially in part 1 of the study. In Arm C, treatment-naive pts with stage IIIB/IV NSCLC received 4 cycles of nab-P 100 mg/m on days 1, 8, and 15 plus C AUC 6 on day 1 of a 21 day cycle in combination with nivolumab 5 mg/kg on day 15 starting at cycle 1. Enrollment for Arm D starts after Arm C is deemed safe to expand. The same regimen will be given in Arm D; however, nivolumab will be given starting cycle 3. In both NSCLC arms, nivo monotherapy begins at cycle 5.

Quality of life (QoL) in patients (pts) with squamous (SCC) NSCLC treated with nab-paclitaxel with carboplatin (nab-P/C) induction therapy: Interim analysis of the phase III ABOUND.sqm study.

64 Background: Recent data on QoL in pts with advanced NSCLC treated with platinum-doublets are limited. This interim analysis evaluated QoL in pts with SCC NSCLC treated with nab-P/C during the induction part of the ABOUND.sqm study. METHODS In the ongoing phase III ABOUND.sqm study, pts with advanced SCC NSCLC are treated with first-line nab-P 100 mg/m2 d 1, 8, 15 and C AUC 6 mg•min/mL d 1 (21-d cycles) for 4 cycles (induction). Pts not progressing after 4 cycles are randomized 2:1 to maintenance nab-P 100 mg/m2d 1 and 8 of each 21-d cycle + best supportive care (BSC) or BSC alone until progression. The primary endpoint is PFS from randomization to maintenance. QoL, an exploratory endpoint, was assessed using predefined PRO instruments, LCSS and EQ-5D-5L, on d 1 of each cycle. As the study is ongoing, this pre-planned analysis included data for QoL that were reported up to the cutoff date. RESULTS Of 128 pts included in this interim analysis, > 80% completed baseline (BL) + ≥ 1 post-BL PRO assessments. The median age was 68 years, 65% were male, and 99% had an ECOG PS of 0-1. Overall, the symptom burden index and average total score of the LCSS PRO were improved during induction therapy with nab-P/C; ≈ 50% of pts had clinically meaningful improvements (≥ 10 mm [VAS]) from BL in the composite LCSS items of cough, shortness of breath, and hemoptysis. More than 80% of pts maintained or improved each dimension of the EQ-5D-5L from BL, and a substantial proportion reported complete resolution of ≥ 1 specific dimension problem during induction (33%-48%; Table). No unusual safety signals were observed. CONCLUSIONS This interim analysis demonstrates that QoL was maintained or improved in pts with SCC NSCLC during nab-P/C induction therapy. For pts who reported problems in EQ-5D-5L dimensions at BL, many achieved complete resolution at least once during chemotherapy. CLINICAL TRIAL INFORMATION NCT02027428. [Table: see text].

Abstract CT141: Phase I study of nivolumab (nivo) +nab-paclitaxel (nab-P) + carboplatin (C) in advanced NSCLC: safety and efficacy results

Background: Chemotherapy leads to tumor lysis and release of tumor antigens, which may prime the immune system for checkpoint inhibitors. The combination of a taxane + immune checkpoint inhibitor has been reported to improve response in non-small cell lung cancer (NSCLC; Giaccone et al. ESMO 2015 [abstract 247]). This analysis provides interim results from the first of the 2 lung cohorts of a phase I study of nivo with the standard dose and schedule of nab-P/C. Methods: The 2 lung cohorts (Arms C and D) were initiated sequentially in part 1 of the study. In Arm C, patients (pts) with stage IIIB/IV NSCLC and no prior chemotherapy for metastatic disease received 4 cycles of nab-P 100 mg/m2 on days 1, 8, and 15 + C area under the curve 6 on day 1 of a 21-day cycle in combination with nivo 5 mg/kg on day 15 starting at cycle 1. Nivo was continued as monotherapy at cycle 5. The same regimen was administered in Arm D, with nivo starting at cycle 3.The primary objective of part 1 was the number of dose-limiting toxicities (DLTs) in each treatment arm, including grade 3/4 treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Pts treated with ? 2 cycles of nivo + nab-P/C or who discontinued due to DLT after the start of nivo and prior to completing 2 cycles of nivo + nab-P/C were considered DLT evaluable. If deemed safe per DLT evaluation, the treatment arms may be expanded to further assess safety, tolerability, and antitumor activity. Results: As of Nov 9, 2015, 12 pts had been enrolled in Arm C; of these, 9 received nivo + nab-P/C before the data cut off date. Overall, most pts were aged ? 65 years (67%) and female (58%); 58% had adenocarcinoma, and 42% had squamous cell carcinoma. No DLTs were observed. The most frequent grade ? 3 TEAEs common to all treated pts and, separately, those treated with nivo + nab-P/C were neutropenia (25% and 22%) and hypokalemia (17% and 22%, 2 out of 3 pts had history of thyroid disorder). No pneumonitis has been reported to date. Of the 9 nivo-treated, response evaluable pts, 6 had a partial response, and 3 had stable disease (SD). In pts not receiving nivo, 1 patient had SD. Overall tumor burden decrease from baseline in total length of target lesions of responding pts ranged from 31% to 83%. Two pts discontinued treatment prior to nivo administration (1 due to AEs and 1 due to voluntary withdrawal); 1 additional pt received nivo after the data cut off date. One pt discontinued due to progression after 23 weeks of nivo + nab-P/C. No treatment-related deaths have been reported to date. Conclusions: In Arm C of the lung cancer cohort, the addition of nivo on day 15 to the standard dose and schedule of nab-P/C did not appear to result in added toxicity or raise new safety/tolerability concerns. Preliminary assessments of antitumor activity were encouraging. Expansion of this treatment arm to further assess safety and tolerability is underway and will be updated (NCT02309177). Citation Format: David M. Waterhouse, Ben George, Martin Gutierrez, Greg A. Otterson, Amy Ko, Teng Jin Ong, Sotirios Stergiopoulos, Nataliya Trunova, Karen Kelly. Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) + carboplatin (C) in advanced NSCLC: safety and efficacy results. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT141.