Plinabulin Plus Nivolumab and Ipilimumab Shows Limited Clinical Benefit for Recurrent Small Cell Lung Cancer

According to results from the multicenter, phase 1/2 BTCRC-LUN17-127 trial, while plinabulin, a GEF-H1 releasing agent with an immune-enhancing function, in combination with nivolumab and ipilimumab was well tolerated among patients with recurrent small cell lung cancer (SCLC), the combination showed limited clinical benefit. 

In phase 1 of this multicenter study, researchers enrolled 16 patients, using a 3 plus 3 design, to receive 1 mg/kg of nivolumab plus 3 mg/kg of ipilimumab and escalating doses of plinabulin (administered on day 1 of each 21-day cycle for up to 4 cycles) followed by maintenance plinabulin and nivolumab. This phase of the trial was to determine dose-limiting toxicities and the recommended phase 2 dose. In phase 2, researchers enrolled 20 patients with recurrent, PD-L1 inhibitor–resistant SCLC with efficacy end points including median progression-free survival (PFS), clinical benefit rate, overall survival (OS), and safety. 

At the time of analysis for phase 1, there were 2 grade 3 dose-limiting toxicities observed (altered mental status lasting < 24 hours and infusion reaction) and 30 mg/m² was identified as the recommended phase 2 dose of plinabulin. Median efficacy follow-up was 2.5 months, including 27 patients. At that time, median PFS was 1.6 months which did not meet the pre-specified target median PFS of 3.5 months. Four patients achieved partial response (1 confirmed and 3 unconfirmed), and 5 patients had stable disease with a clinical benefit rate of 33%. The median OS was 5.5 months. 

The most frequent treatment-related adverse events included vomiting (44%), nausea (42%), and infusion reaction (36%). Grade ≥3 treatment-related adverse events were observed in 6% of patients. Grade ≥3 immune-related adverse events were observed in 14% of patients. There were no cases of immune-related pneumonitis.

“Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m²,” concluded Dr Malhotra et al. “While the clinical responses in PD-1–resistant SCLC were limited, some patients had a long duration of response [and] the number of ≥ grade 3 [immune-related adverse events] with the combination were lower than expected.” 

Source: 

Malhotra J, Chiappori A, Fujioka N, et al. Phase I/II trial of plinabulin in combination with nivolumab and ipilimumab in patients with recurrent small cell lung cancer (SCLC): Big ten cancer research consortium (BTCRC-LUN17-127) study. Lung Cancer. Published online: August 15, 2024. doi: 10.1016/j.lungcan.2024.107932