Abstract 1056P
Background
D (anti-PD-L1) has shown clinical activity and a manageable safety profile in patients (pts) with advanced solid tumours as monotherapy, in combination with cisplatin (cis)/carboplatin (car)-based chemotherapy, and post-CRT. CLOVER (NCT03509012) is a phase 1, open-label, multicentre study evaluating D ± tremelimumab (T) in combination with CRT for pts with locally advanced HNSCC (cis eligible); unresectable, stage III NSCLC; or limited-stage SCLC (LS-SCLC). Here we present safety results from the D + CRT arms in part A (dose-limiting toxicities [DLTs] assessment phase).
Methods
Pts aged ≥ 18 yrs, WHO PS 0/1 and no prior immunotherapy were enrolled in three cohorts. HNSCC: D + cis + RT; NSCLC: D + cis + etoposide (EP) + RT (arm 1); D + car + paclitaxel + RT (arm 2); or D + pemetrexed + car or cis (investigator’s choice) + RT (arm 3); LS-SCLC: D + EP + RT (arm 1); D + EP + hyperfractionated RT (arm 2); D + T + EP + RT (arm 3); or D + T + EP + hyperfractionated RT (arm 4). Primary endpoint (part A): safety, including DLTs. Part B will assess safety and efficacy in expanded arms.
Results
Eight pts were treated with D + CRT in the HNSCC cohort, 19 in the NSCLC cohort, and 13 in the LS-SCLC cohort. One pt in the NSCLC cohort had a DLT (grade 3/4 transaminitis; arm 1). Safety is summarized in the table. Most common grade 3/4 AEs were lymphopenia, stomatitis, leukopenia and elevated amylase in the HNSCC cohort, and neutropenia, leukopenia and anaemia in the NSCLC and LS-SCLC cohorts. One pt died due to acute kidney injury in the HNSCC cohort, and 3 pts died in total in the NSCLC cohort due to pneumocystis jirovecii pneumonia (arm 1), acute coronary syndrome (arm 2) and cardiac arrest (arm 3). Preliminary efficacy data will be presented. Table: 1056P
| HNSCC N=8 | NSCLC N=19 | LS-SCLC N=13 | ||||
| Arm 1 n=6 | Arm 2 n=7 | Arm 3 n=6 | Arm 1 n=7 | Arm 2 n=6 | ||
| Any AEs, n (%) | 8 (100) | 6 (100) | 7 (100) | 6 (100) | 7 (100) | 6 (100) |
| Gr 3/4 AEs | 7 (87.5) | 5 (83.3) | 7 (100) | 4 (66.7) | 7 (100) | 6 (100) |
| Serious AEs | 2 (25.0) | 5 (83.3) | 5 (71.4) | 1 (16.7) | 1 (14.3) | 1 (16.7) |
| AEs leading to treatment discontinuation | 2 (25.0) | 2 (33.3) | 2 (28.6) | 1 (16.7) | 1 (14.3) | 0 |
| Immune-related AEs* | 3 (37.5) | 3 (50.0) | 5 (71.4) | 3 (50.0) | 4 (57.1) | 2 (33.3) |
*Assessed by the investigator.
Conclusions
In CLOVER, D in combination with CRT was generally well tolerated in pts with locally advanced HNSCC, unresectable, stage III NSCLC, and LS-SCLC, with only 1 DLT in the NSCLC cohort. The high rate of grade 3/4 AEs was similar to historical data of CRT used as backbone therapy in these indications.
Clinical trial identification
NCT03509012; April 26, 2018.
Editorial acknowledgement
Medical writing support, in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca PLC.
Funding
AstraZeneca.
Disclosure
J.E. Bauman: Non-remunerated activity/ies, To institution: investigator-initiated clinical trial (drug only): Novartis; Non-remunerated activity/ies, To institution: investigator-initiated clinical trial (drug only): Lilly; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Aveo; Research grant/Funding (institution): Moderna; Research grant/Funding (institution): Cue. S.D. Karam: Research grant/Funding (institution): AstraZeneca. M. Nishio: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD, Novartis, Takeda Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer-Ingelheim, Merck Biopharma, Teijin Pharmaceutical, AbbVie, Daiichi Sankyo. M-J. Ahn: Advisory/Consultancy: AstraZeneca, Lilly, MSD, BMS, Takeda, Roche, Merck, Alpha Pharmaceutical. D-W. Kim: Travel/Accommodation/Expenses: Amgen, Daiichi-Sankyo; Research grant/Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Boehringer-Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD; Research grant/Funding (institution): Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. H. Murakami: Travel/Accommodation/Expenses, Personal fees: Ono Pharmaceutical, MSD, Bristol-Myers Squibb Japan; Research grant/Funding (institution): AbbVie, Daiichi Sankyo, IQVIA; Research grant/Funding (institution), Research funding and additional personal fees: AstraZeneca, Chugai Pharma, Lilly Japan, Taiho Pharmaceutical, Takeda. L. Wang, J. Shetty: Full/Part-time employment: AstraZeneca. K.Y. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. P.A. Dennis: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. B.C. Cho: Officer/Board of Directors, Founder: Daan Biotherapeutics; Licensing/Royalties, Royalties: Champions Oncology; Shareholder/Stockholder/Stock options: TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, Kanaph Therapeutic Inc; Advisory/Consultancy: Kanaph Therapeutic Inc, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly; Advisory/Consultancy: Takeda, MSD, Janssen, Medpacto, Blueprint Medicines; Research grant/Funding (institution): Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen; Research grant/Funding (institution): Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint Medicines. All other authors have declared no conflicts of interest.