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
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Lung Cancer
- Sponsor
- Salma Sabbour
- Enrollment
- 39
- Locations
- 8
- Primary Endpoint
- Phase I: Maximum Tolerated Dose (MTD)
- Status
- Completed
- Last Updated
- 3 months ago
Overview
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.
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.
Investigators
Salma Sabbour
Sponsor Investigator
Big Ten Cancer Research Consortium
Eligibility Criteria
Inclusion Criteria
- •The patients must satisfy all of the following inclusion/
Exclusion Criteria
- •in order to be eligible for the study:
- •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.
Arms & Interventions
Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin
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
Intervention: Nivolumab
Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin
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
Intervention: Plinabulin
Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin
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
Intervention: Ipilimumab
Phase II: nivolumab, ipilimumab, and plinabulin
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 .
Intervention: Nivolumab
Phase II: nivolumab, ipilimumab, and plinabulin
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 .
Intervention: Plinabulin
Phase II: nivolumab, ipilimumab, and plinabulin
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 .
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Phase I: Maximum Tolerated Dose (MTD)
Time Frame: Up to 42 days of first Plinabulin dose
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.
Progression-Free Survival (PFS)
Time Frame: Up to maximum of 9 months
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.
Secondary Outcomes
- 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)
- Overall Survival(Up to a maximum of 45 months)