Abstract CT286: CANOPY program clinical trials: Canakinumab (Cana) in patients (pts) with non-small cell lung cancer (NSCLC)
Authors: Paz-Ares Luis , Garon Edward B. , Mok Tony , Ardizzoni Andrea , Barlesi Fabrice , Cho Byoung Chul , de Castro Gilberto , De Marchi Pedro , Felip Enriqueta , Goto Yasushi , Greystoke Alastair , Lu Shun , Lim Darren Wan-Teck , Reck Martin , Solomon Benjamin J. , Spigel David R. , Tan Daniel SW , Thomas Michael , Yang James Chih-Hsin , Lee Jay M. , Garrido Pilar , Kim Edward , Johnson Bruce E. 
Published: September 2020

Background: In the CANTOS study, treatment (tx) with Cana (selective IL-1β inhibitor) was associated with reduced incidence and mortality of NSCLC in stable post-myocardial infarction pts with elevated high-sensitivity C-reactive protein levels. The results provided a rationale to investigate the therapeutic role of Cana in NSCLC. Methods: The phase (ph) 2, open-label CANOPY-N study (NCT03968419) is evaluating Cana or pembrolizumab (pembro) alone or in combination as neoadjuvant tx in stage IB-IIIA, tx-naive NSCLC pts eligible for primary resection (except N2 and T4 tumors) with planned surgery in 4-6 weeks (wks) from the 1st dose of study tx. Pts (~110) are randomized 2:2:1 to Cana (2 doses 200 mg SC Q3W), Cana + pembro, or pembro (2 doses 200 mg iv Q3W) for 2 three-wk cycles. Randomization (R) stratification: histology (squamous [sq] vs non-sq). Primary endpoint: major pathological response rate at time of surgery.CANOPY-A (NCT03447769), CANOPY-1 (NCT03631199), and CANOPY-2 (NCT03626545) are ph 3, multicenter, double-blind studies. In CANOPY-A (Cana in adjuvant setting), pts (~1500) with stages IIA-IIIA and IIIB (T&gt;5 cm N2), any histology, completely resected (R0) NSCLC post cisplatin-based chemotherapy (CTx) and radiation therapy (if applicable) are randomized 1:1 to Cana (200 mg SC Q3W)/placebo (PBO; SC Q3W) for 18 cycles. R stratification: AJCC/UICC v.8 stage (IIA vs IIB vs IIIA vs IIIB with T&gt;5 cm, N2 disease), histology (sq vs non-sq), region (western Europe and North America vs eastern Asia vs rest of the world). Primary endpoint: disease-free survival. CANOPY-1 and CANOPY-2 consist of Part 1 (open-label, safety run-in; enrollment complete) and Part 2 (randomized 1:1, PBO-controlled, efficacy & safety; ongoing). CANOPY-1 eligibility: pts with previously untreated stages IIIB/IIIC or IV NSCLC and known PD-L1 status (for Part 2), without EGFR sensitizing mutations and/or ALK rearrangements. Part 1 (3 cohorts of ~9 pts each, based on different platinum-CTx): to confirm the recommended phase 3 regimen (RP3R) for Cana. In Part 2, pts (~600) are randomized to Cana (200 mg SC Q3W)/PBO + pembro + CTx for 4 cycles, followed by maintenance tx (Cana/PBO + pembro ± pemetrexed) until progressive disease (PD). R stratification: PD-L1 status (tumor proportion score &lt;1% vs ≥1%), histology (sq vs non-sq), geographic region (eastern Asia vs North America + western Europe vs rest of the world). Screening has ceased as of Dec 9, 2019. In CANOPY-2, pts with stage IIIB-IV NSCLC, who received prior PD-(L)1 inhibitor therapy and platinum-based CTx, without EGFR sensitizing mutations and/or ALK rearrangements are eligible. Part 1 (~9 pts): to confirm the RP3R of Cana + docetaxel. In Part 2, pts (~226) are randomized to receive Cana (200 mg SC Q3W)/PBO + docetaxel (75 mg/m2 iv Q3W) until PD. R stratification: number of prior lines of therapy in advanced setting (1 vs 2 prior lines of therapy) and histology (sq vs non-sq). Primary endpoints: CANOPY-1 and CANOPY-2 Part 1: to confirm RP3R of the combination; CANOPY-1 Part 2: progression-free survival and overall survival (OS); CANOPY-2 Part 2: OS.

Citation Format: Luis Paz-Ares, Edward B. Garon, Tony Mok, Andrea Ardizzoni, Fabrice Barlesi, Byoung Chul Cho, Gilberto de Castro, Pedro De Marchi, Enriqueta Felip, Yasushi Goto, Alastair Greystoke, Shun Lu, Darren Wan-Teck Lim, Martin Reck, Benjamin J. Solomon, David R. Spigel, Daniel SW Tan, Michael Thomas, James Chih-Hsin Yang, Jay M. Lee, Pilar Garrido, Edward Kim, Bruce E. Johnson. CANOPY program clinical trials: Canakinumab (Cana) in patients (pts) with non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT286.