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

NCT03575793 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BTCRC-LUN17-127
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Lung Cancer; SCLC

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose (MTD)

  Establish MTD of plinabulin in combination with nivolumab and ipilimumab for patients with recurrent SCLC. MTD reflects the highest dose of plinabulin that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined in accordance to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

  Up to 42 days of first Plinabulin dose

• Progression-Free Survival (PFS)

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease(PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression Free Survival (PFS) is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.

  Up to maximum of 9 months

Secondary Outcomes (6)

• Number of Participants With Adverse Events

  Up to a maximum of 43 months

• Number of Participants With Immune-related Adverse Events (irAEs)

  Up to a maximum of 43 months

• Objective Response Rate (ORR)

  Up to maximum of 9 months

• Clinical Benefit Rate

  Up to maximum of 9 months

• Progression Free Survival at 6 Months

  6 Months

Study Arms (2)

Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin

EXPERIMENTAL

On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2

Drug: Nivolumab; Drug: Plinabulin; Drug: Ipilimumab

Phase II: nivolumab, ipilimumab, and plinabulin

EXPERIMENTAL

On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (MTD from Phase I). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur .

Drug: Nivolumab; Drug: Plinabulin; Drug: Ipilimumab

Interventions

Nivolumab DRUG

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.

Also known as: Opdivo

Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin; Phase II: nivolumab, ipilimumab, and plinabulin

Plinabulin DRUG

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).

Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin; Phase II: nivolumab, ipilimumab, and plinabulin

Ipilimumab DRUG

Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

Also known as: Yervoy

Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin; Phase II: nivolumab, ipilimumab, and plinabulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines.
• Males and females aged \>18 years at time of consent.
• Histological or cytological confirmed extensive-stage SCLC
• Patients who progressed after at least 1 platinum-based chemotherapy regimen. Patients with platinum resistance (defined as recurrence or progression of disease within 90 days of completion of the platinum-based regimen) are eligible. For phase II, patients also must have been treated with at least one prior line of PD-1/PD-L1 therapy.
• Measurable disease according to RECIST v1.1 (Section 8) obtained by imaging within 28 days prior to study registration.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before registration and minimum life expectancy of at least 12 weeks.
• Treatment to be initiated at least 2 weeks since last dose of prior systemic anticancer therapy (chemotherapy, radiation, and/or surgery.
• Recovery to grade 1 of any clinically significant toxicity (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy) prior to initiation of study drugs.
• Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti estrogens, or ovarian suppression.
• Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within 14 days of study registration and within the 24-hour period prior to the first dose of study drug.
• Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 23 weeks after their last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner.
• For male patients who are sexually active and who are partners of premenopausal women: agreement to use 2 forms of contraception as in criterion 9b above during the treatment period and for 31 weeks after the last dose of study drug.
• Adequate laboratory values.
• Absolute neutrophil count ≥1,000/µL
• Platelet count ≥100,000/µL

Sponsors & Collaborators

• BeyondSpring Pharmaceuticals Inc.: collaborator
• Bristol-Myers Squibb: collaborator
• Rutgers Cancer Institute of New Jersey: collaborator
• Salma Sabbour: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Erlanger Health System

Chattanooga, Tennessee, 37403, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Nivolumab; NPI 2358; Ipilimumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Salma Jabbour, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: July 3, 2018
• Study Start: September 6, 2018
• Primary Completion: September 25, 2023
• Study Completion: July 1, 2024
• Last Updated: January 20, 2026
• Results First Posted: November 12, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)