September 4, 2024:

A Big Ten Cancer Research Consortium (Big Ten CRC) study manuscript was published in Lung Cancer Journal on August 15, 2024. The article is titled, “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.”  

Congratulations to all co-authors and study teams whose hard work led to this publication.

Abstract:

Plinabulin is a GEF-H1 releasing agent with an immune-enhancing function. We report results from a multicenter Phase I/II study (NCT03575793) assessing plinabulin in combination with nivolumab and ipilimumab for the treatment of recurrent SCLC.

In Phase I, patients were enrolled using a 3 + 3 design to determine dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D). Patients received nivolumab (1 mg/kg), ipilimumab (3 mg/kg), and plinabulin (in escalating doses) on day 1 of each 21-day cycle for 4 cycles followed by maintenance with plinabulin and nivolumab. In phase II, patients with recurrent PD(L)1 inhibitor resistant SCLC were enrolled. The primary objective was median progression-free survival (PFS).

Between 9/2018 and 2/2023, 39 patients were enrolled, and 36 patients received study treatment and were evaluable for safety (16 in Phase I; 20 in Phase II). In the phase I dose-escalation, there were 2 DLTs; grade 3 altered mental status lasting <24 h and grade 3 infusion reaction. The Plinabulin RP2D was determined to be 30 mg/m². Common TRAEs were vomiting (44 %), nausea (42 %), and infusion reaction (36 %); 6 % of patients had a ≥grade 3 TRAE. Five patients (14 %) had ≥grade 3 irAEs; there were no cases of immune-related pneumonitis. In the efficacy analysis in 27 patients, the median PFS was 1.6 months (95 % CI 1.2 to 2.7) and the trial did not meet the pre-specified target median PFS of 3.5 months. Four patients treated at 30 mg/m² had PR (confirmed 1, unconfirmed 3); 5 patients had SD with a CBR of 33 %. Two of 8 patients treated in phase I at the lower 20 mg/m² dose had confirmed PR, with 1 patient on the drug regimen for >90 cycles. The median OS and follow-up time were 5.5 months and 2.5 months respectively.

Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m². While the clinical responses in PD-1 resistant SCLC were limited, some patients had a long duration of response. The number of ≥grade 3 irAE with the combination were lower than expected.

Read the full article.

Authors:

Jyoti Malhotra (City of Hope National Medical Center), Alberto Chiappori (H. Lee Moffitt Cancer Center and Research Institute), Naomi Fujioka (University of Minnesota), Nasser H. Hanna (Indiana University Melvin and Bren Simon Comprehensive Cancer Center), Lawrence E. Feldman (University of Illinois Hospital & Health Sciences System), Malini Patel (Rutgers Cancer Institute of New Jersey), Dirk Moore (Rutgers Cancer Institute of New Jersey), Chunxia Chen (Rutgers Cancer Institute of New Jersey), and Salma K. Jabbour (Rutgers Cancer Institute of New Jersey).

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative clinical trials and observational studies that seek to improve the lives of cancer patients in the diverse communities we serve by leveraging the scientific and clinical expertise of Big Ten universities. The Big Ten Cancer Research Consortium creates a unique team research culture to drive science rapidly from ideas to treatment and prevention. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow. Since its founding, the Big Ten CRC has activated nearly 40 clinical trials across a wide range of cancer types, more than 1,000 participants have enrolled in Big Ten CRC studies, and more than 500 researchers have joined Big Ten CRC Clinical Trial Working Groups.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 18 Big Ten institutions provide direct financial support for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women. For more information, visit www.bigten.org.