Clinical Trial 20332

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT04610658

Phase: Phase I/II
Principal Investigator: Chiappori, Alberto

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Overview

Study Title

Activity and Enhancement of Immune Checkpoint Inhibition with Lurbinectedin in Relapsed/Recurrent Small Cell Lung Cancer (SCLC)

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

Objective

Primary Objective Phase I (Dose Escalation): To determine the MTD and RP2D of nivolumab-ipilimumab plus lurbinectedin. Primary Objective Phase II (Single Arm Cohort): To determine the efficacy of nivolumab-ipilimumab plus lurbinectedin in patients with relapsed/recurrent SCLC. Secondary Objectives: To further describe efficacy and to further describe safety. Tertiary/Exploratory Objectives: To examine potential predictive markers in the turmors of clinical responders. Characterize the evolution of the immune compartment during treatment. Determine Th1, Th2, and Th17 polarization during treatment with ipilimumab-nivolumab plus lurbinectedin.

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy

Medications

BMS-936558 (Nivolumab); Ipilimumab (); Nivolumab (Opdivo); PM01183 (lurbinectedin); Yervoy (Ipilimumab); lurbinectedin ()

Inclusion Criteria

Inclusion Criteria:

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.

Exclusion Criteria

Exclusion Criteria:

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: (A) History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year. (B) Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment. (C) 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. (D) 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).

Additional exclusions apply

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