Immune Checkpoint Inhibition With Lurbinectedin Relapsed/Recurrent SCLC

NCT04610658 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: MCC-20332
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-arm, phase I/II trial to determine the Maximum Tolerated Dose (MTD), Recommended Phase II Dose (RP2D), and the safety and efficacy of the combination of nivolumab-ipilimumab plus lurbinectedin in patients with relapsed/recurrent small cell lung cancer after progression with first-line, platinum-based chemotherapy

Conditions

Small-cell Lung Cancer; Relapsed Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1: Maximum Tolerated Dose (MTD) of Lurbinectedin with Nivolumab and Ipilimumab

  Maximum tolerated Dose will be determined by testing increasing doses of Lurbinectedin along with fixed doses of Nivolumab and Ipilimumab.

  Up to 12 weeks per cohort

• Phase II: Disease Control Rate

  Disease Control Rate (DCR) is defined as Complete Response (CR) +Partial Response (PR) +Stable Disease (SD). Best response time will be used for this measurement.

  Up to 12 months

Secondary Outcomes (3)

• Overall Response Rate

  Up to 12 months

• Progression Free Survival

  Up to 12 months

• Overall Survival

  Up to 12 months

Study Arms (3)

Phase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin

EXPERIMENTAL

Participants will be treated at dose level 1: nivolumab 1mg/kg, ipilimumab 3mg/kg plus 1.5 mg/m\^2 lurbinectedin. Participants will receive nivolumab, ipilimumab and Lurbinectedin every 3 weeks for 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and participants will continue treatment with a flat dose of 360 mg nivolumab and Lurbinectedin at dose level 1 every 3 weeks.

Drug: Nivolumab; Drug: Ipilimumab; Drug: Lurbinectedin

Phase 1 Dose Level 2: Nivolumab and Ipilimumab plus Lurbinectedin

EXPERIMENTAL

Participants will be treated at dose level 2: nivolumab 1mg/kg, ipilimumab 3mg/kg plus 2.6 mg/m\^2 lurbinectedin. Participants will receive nivolumab, ipilimumab and Lurbinectedin every 3 weeks for 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and participants will continue treatment with a flat dose of 360 mg nivolumab and Lurbinectedin at dose level 2 every 3 weeks.

Drug: Nivolumab; Drug: Ipilimumab; Drug: Lurbinectedin

Phase 1 Dose Level 3: Nivolumab and Ipilimumab plus Lurbinectedin

EXPERIMENTAL

Participants will be treated at dose level 3: nivolumab 1mg/kg, ipilimumab 3mg/kg plus 3.2 mg/m\^2 lurbinectedin. Participants will receive nivolumab, ipilimumab and Lurbinectedin every 3 weeks for 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and participants will continue treatment with a flat dose of 360 mg nivolumab and Lurbinectedin at dose level 3 every 3 weeks.

Drug: Nivolumab; Drug: Ipilimumab; Drug: Lurbinectedin

Interventions

Nivolumab DRUG

Participants will receive 1 mg/kg Nivolumab on Day 1 of each treatment cycle for 4 cycles (induction immunotherapy). After 4 treatment cycles, Nivolumab will be continued at a flat dose of 360 mg.

Also known as: Opdivo

Phase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin; Phase 1 Dose Level 2: Nivolumab and Ipilimumab plus Lurbinectedin; Phase 1 Dose Level 3: Nivolumab and Ipilimumab plus Lurbinectedin

Ipilimumab DRUG

Participants will receive 3mg/kg Ipilimumab on Day 1 of each treatment cycle for 4 cycles (induction immunotherapy). After 4 cycles, Ipilimumab will be discontinued.

Also known as: Yervoy

Phase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin; Phase 1 Dose Level 2: Nivolumab and Ipilimumab plus Lurbinectedin; Phase 1 Dose Level 3: Nivolumab and Ipilimumab plus Lurbinectedin

Lurbinectedin DRUG

Participants will be treated at 1 of 3 dose levels of Lurbinectedin, beginning at 1.5 mg/m\^2 and increasing to 3.2 mg/m\^2 or the Maximum Tolerated Dose (MTD)

Phase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin; Phase 1 Dose Level 2: Nivolumab and Ipilimumab plus Lurbinectedin; Phase 1 Dose Level 3: Nivolumab and Ipilimumab plus Lurbinectedin

Eligibility Criteria

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

You may qualify if:

• Measurable disease based on RECIST v1.1
• Performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Adequate organ function as defined per protocol
• Women of child bearing potential (WOCBP) must have a negative urine or serum pregnancy test within 72 hours from receiving first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• WOCBP should agree to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication, or should be surgically sterile. Note: A woman is considered to be of "reproductive potential" (WOCBP) if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, she is responsible for beginning contraceptive measures.
• Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
• Note: In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (vasectomy). However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, he is responsible for beginning contraceptive measures.

You may not qualify if:

• Individuals meeting any of the following criteria will be excluded from participation in this study:
• Is currently participating in a study of an investigational agent or device and received or used the investigational agent or device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment. Note: Systemic steroid doses of ≤ 10 mg of prednisone daily or its equivalent are allowed in patients receiving physiologic replacement steroid doses
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to Lurbinectedin, Ipilimumab and/or nivolumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had targeted small molecule therapy, or standard fractionated radiotherapy within 2 weeks, chemotherapy within 3 weeks and stereotactic radiotherapy within 1 week prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note:: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Other malignancies that remain without evidence of disease or recurrence, 2 years or more after curative therapy are also considered part of this exception.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 2 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has any of the following concomitant diseases/conditions:
• History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
• Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
• History of idiopathic, pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis or evidence of active pneumonitis on screening chest CT-scan. History of radiation pneumonitis in radiation field (fibrosis) is permitted, as long as it is asymptomatic and no steroids are needed.
• Myopathy or any clinical situation that causes significant and persistent elevation of CPK (\>2.5 x upper limit of normal (ULN) in two different determinations performed one week apart).
• Any diagnosis of autoimmune disease (confirmed by medical records or appropriate laboratory testing) is not allowed.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator
• Jazz Pharmaceuticals: collaborator

Study Sites (2)

Advent Health - Celebration

Kissimmee, Florida, 34747, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Nivolumab; Ipilimumab; PM 01183

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; 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

Study Officials

• Alberto A Chiappori, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 30, 2020
• Study Start: November 23, 2020
• Primary Completion: March 24, 2023
• Study Completion: March 24, 2023
• Last Updated: April 2, 2024

Record last verified: 2024-04

Locations

US (2)