NCT03575793

A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer

A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer: Big Ten Cancer Research Consortium. BTCRC-LUN17-127

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: Salma Sabbour · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label Phase I/II study, with a dose escalation part (Phase I) and a single-arm part (Phase II), in patients with recurrent SCLC who progressed after first-line platinum-based chemotherapy and who are candidates for second line therapy. No PK evaluation is planned in this study as nivolumab and ipilimumab are unlikely to alter plinabulin's PK, since the route of excretion is different.

Detailed description

This is an open-label Phase I/II study, with a dose escalation part (Phase I) and a single arm part (Phase II), in patients with recurrent SCLC. In the Phase I part, patients will receive plinabulin at escalating doses in combination with nivolumab and ipilimumab. Doses of study drug will be administered as intravenous (IV) infusions in 21 day cycles. Patients will receive all study drugs on Day 1 of each cycle. After 4 treatment cycles, ipilimumab is stopped and patients continue treatment with nivolumab and plinabulin every 2 weeks (maintenance period) or until disease progression, development of unacceptable toxicity or one of the protocol-defined reasons for treatment discontinuation occurs. At least 3 patients will be enrolled in each cohort, starting at 20 mg/m2 of plinabulin. The dose of plinabulin will be escalated in sequential patient cohorts after the safety data from the first cycle is reviewed. Thereafter the dose of plinabulin will be escalated to 30 mg/m2, provided that dose-limiting toxicities (DLTs) are not observed per the specified criteria, until the RP2D is determined. In the Phase II part, up to 26 patients will be treated with the triple combination of plinabulin (at RP2D) + nivolumab + ipilimumab. Patients will continue treatment until disease progression, development of unacceptable toxicity or one of the protocol-defined reasons for treatment discontinuation occurs.

Conditions

• Lung Cancer
• SCLC

Interventions

Type	Name	Description
DRUG	Nivolumab	A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities.
DRUG	Plinabulin	Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin).
DRUG	Ipilimumab	Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

Timeline

• Start date: 2018-09-06
• Primary completion: 2023-09-25
• Completion: 2024-07-01
• First posted: 2018-07-03
• Last updated: 2026-01-20
• Results posted: 2024-11-12

Locations

8 sites across 1 country: United States

Regulatory

• FDA-regulated drug study