Final results from a phase II trial of CIMAvax-EGF and nivolumab as second-line (2L) therapy after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).
Authors: Frascati Rachel , Early Amy P. , Reid Mary E. , Lee Kelvin , Muhitch Jason , Mesa Circe , Luaces Patricia Lorenzo , Santos-Morales Orestes , Dozier Askia , Puzanov Igor , Fountzilas Christos , Gandhi Shipra , Attwood Kristopher , Hutson Alan , Johnson Candace S. , Herrera Zaima , Saavedra Danay , Leon Kalet , Crombet Ramos Tania , Dy Grace K. 
Published: June 2023

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Background: CIMAvax-EGF (C-E) is a recombinant anti-human epidermal growth factor (EGF) depleting immunotherapy which has previously shown increased survival as maintenance after platinum-based chemotherapy in patients (pts) with advanced NSCLC. The primary objective of this single-arm phase II trial was to evaluate the 12-month overall survival (OS) in pts receiving C-E in combination with Nivolumab(N) as 2L therapy for advanced NSCLC. Methods: Pts with previously treated, immunotherapy-naive advanced NSCLC received 2.4 mg C-E IM every 2 weeks(w) for 4 doses (loading phase) in combination with N 240mg IV every 2 w, then continued monthly maintenance C-E combined with N 240mg IV every 2 w. Enrollment to this arm was terminated before estimated sample size was met due to poor accrual as immunotherapy became incorporated into 1st line therapy. We present OS and progression-free survival (PFS) data [determined using a Kaplan-Meier test with 90% confidence intervals (CI)] of pts who were able to complete the loading phase per protocol (PP). Results: 21 out of 23 enrolled pts were included in the PP analysis. Among the 21 pts, 17 (81.0%) had non-squamous(nsq) histology, 12 (57.1%) were KRAS wildtype (9.5% unknown status), 13 (61.9%) had PD-L1 tumor proportion score 0%. 43% pts (n=3) with known KRAS mutation (n=7) had co-mutated STK11. Disease control rate was 47.6% (n=10) defined as pts who had stable disease or partial response as best response per RECIST v1.1. The 21 PP pts had a 29% 3-year(yr) OS rate (90% CI 14, 45; intention-to-treat [ITT] population in 23 pts with 26% 3-yr OS rate, 90% CI 13, 42). Median(m) OS for PP pts was 11.9 months, 90% CI 8.0 – 23.9 months (ITT mOS 10.4 months, 90% CI 6.8-13.6). Pts with squamous histology had a better 3-yr OS rate compared to those with nsq histology [50% (90% CI 10, 81) vs 24% (90% CI 9, 41), respectively]. Pts with PD-L1 expression ≥1% had higher 3-yr OS [38% (90% CI 12, 63)] and 3-year PFS [38% (90% CI 12, 63)] compared to pts with no PD-L1 expression (3-yr OS 23% [90% CI 8, 44] and 3-yr PFS 8% [90% CI 1, 25]). mOS, 1-yr and 3-yr OS for EGFR/ALK/KRAS wildtype pts was higher [31.7 months (90% CI 5.9, NR), 67% (90% CI 4, 84), 50% (90% CI 24,71), respectively) compared to KRAS mutated NSCLC [10.1 months (90% CI 6.5, 12.1), 29% (90% CI 6, 56), 0% (90% CI 1, 41), respectively]. Conclusions: NSCLC pts who were able to complete the PP combination of C-E plus N at the minimum had numerically better OS compared to historical study cohorts with N as 2L monotherapy. Among pts who completed PP treatment, pts with KRAS wildtype NSCLC had the longest mOS observed. C-E is currently being investigated in combination with pembrolizumab as maintenance therapy after completing 1L chemoimmunotherapy for NSCLC with PD-L1 < 50% and as 1L therapy in combination with pembrolizumab for EGFR/ALK wildtype NSCLC and PD-L1 ≥ 50%. Clinical trial information: NCT02955290 .