Meeting
2019 ASCO Annual Meeting
A randomized phase II study of tremelimumab and durvalumab with or without radiation for patients with relapsed small cell lung cancer (SCLC).
Authors
Taofeek Kunle Owonikoko
Emory University, Atlanta, GA
Taofeek Kunle Owonikoko , Kristin Ann Higgins , Zhengjia Chen , Chao Zhang , Rathi Narayana Pillai , Conor Ernst Steuer , Nabil F. Saba , Suchita Pakkala , Dong Moon Shin , Guojing Zhang , Shuhua Wang , Mohammed S Hossain , Tyler Beardslee , Anne Engelhart , Janine Revenig , Fadlo Khuri , Walter John Curran, Jr. Jr., Sagar Lonial , Edmund K. Waller , Suresh S. Ramalingam
Organizations
Emory University, Atlanta, GA, Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, Emory University Winship Cancer Institute, Atlanta, GA, Winship Cancer Institute of Emory University, Atlanta, GA, Emory Clinic, Atlanta, GA, Emory Winship Cancer Institute, Atlanta, GA, The Winship Cancer Institute of Emory University, Atlanta, GA, Winship Cancer Institute, Emory University, Atlanta, GA
Research Funding
Pharmaceutical/Biotech Company
Background: The combination of PD-1 and CTLA-4 inhibition has demonstrated activity in the second line therapy setting for SCLC. Radiotherapy enhanced the effectiveness of immunotherapy in NSCLC. We conducted this signal finding study to assess the efficacy of combined ICI with or without radiation in relapsed SCLC. Methods: Patients with relapsed SCLC who have received not more than 2 lines of therapy were enrolled and randomized to either Arm A: [Tremelimumab (T) 1500mg/durvalumab (D) 75mg i.v. every 4 weeks without SBRT] or Arm B: T/D with immune sensitizing SBRT to one selected tumor site (9 Gy x 3 fractions). Treatment continued until progression or maximum of 2 years. Paired tumor biopsies and serial samples of peripheral blood were employed for correlative endpoints (changes in intratumoral and circulating lymphocyte repertoire and immune cytokines). The study was designed to show a promising efficacy signal in either Arm with a hypothesized median PFS of 7 months (10 patients give 87% power at 1-sided alpha of 0.1). Results: Study randomized 17 patients to Arm A (8 patients) or B (9 patients); median age of 70 yrs; females 41.2%; White, 70%, Black 17.6%. Best response in 14 overall evaluable patients was PD in 9 (64.3%), PR in 2 (14%) and SD in 3 (21.4%); median PFS of 2.76 months and OS of 4.47 months. There was no significant difference in efficacy between Arms A and B but a trend of improved PFS and OS with T/D plus SBRT (see table): Median PFS of 2.1 vs. 3.3 months [HR: 2.44 (0.75-7.93); p = 0.122] and median OS of 2.6 vs. 5.7 months [HR: 1.50 (0.45-4.99); p = 0.5068]. Observed grade ≥ 3 adverse events were: Cytopenia (4), Dyspnea (1), and endocrine disorders (3) in Arm A; diarrhea (3) and cytopenias (1) in Arm B. There was an increase in circulating CD8(+) lymphocytes on treatment versus baseline in patients with objective tumor response. Conclusions: The study did not show sufficient signal of efficacy for ICI with or without SBRT in relapsed SCLC. Detailed result of the biomarker analysis will be available at the meeting. Clinical trial information: NCT02701400
| Covariate | Statistics | Level | Study_Arm | P-value | |
|---|---|---|---|---|---|
| Arm A N = 8 | Arm B N = 7 | ||||
| Gender | N (Row %) | F | 3 (50) | 3 (50) | 1.000 |
| M | 5 (55.56) | 4 (44.44) | |||
| Race | N (Row %) | Black or African American | 0 (0) | 3 (100) | 0.128 |
| Unknown | 1 (100) | 0 (0) | |||
| White | 7 (63.64) | 4 (36.36) | |||
| Ethnicity | N (Row %) | Non-Hispanic | 8 (53.33) | 7 (46.67) | |
| Age (Yrs) | Mean | 70.5 | 66.86 | 0.407 | |
| Best Response | N (Row %) | PD | 5 (55.56) | 4 (44.44) | 0.559 |
| PR | 0 (0) | 2 (100) | |||
| SD | 2 (66.67) | 1 (33.33) | |||
| PFS (months) | Median | 2.1 | 3.3 | ||
| HR (95% CI) | 2.44 (0.75-7.93) | 0.122 | |||
| OS (months) | Median | 2.6 | 5.7 | ||
| HR (95% CI) | 1.50 (0.45-4.99) | 0.507 | |||
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Abstract Details
Session Type
Poster Discussion Session
Session Title
Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Track
Lung Cancer
Sub Track
Small Cell Lung Cancer
Clinical Trial Registration Number
NCT02701400
Citation
J Clin Oncol 37, 2019 (suppl; abstr 8515)
DOI
10.1200/JCO.2019.37.15_suppl.8515
Abstract #
8515
Poster Bd #
271
Abstract Disclosures
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