Clinical Trials /

Immune Checkpoint Inhibition With Lurbinectedin Relapsed/Recurrent SCLC

NCT04610658

Description:

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

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Immune Checkpoint Inhibition With Lurbinectedin Relapsed/Recurrent SCLC
  • Official Title: Activity and Enhancement of Immune Checkpoint Inhibition With Lurbinectedin in Relapsed/Recurrent Small Cell Lung Cancer (SCLC)

Clinical Trial IDs

  • ORG STUDY ID: MCC-20332
  • NCT ID: NCT04610658

Conditions

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

Interventions

DrugSynonymsArms
NivolumabOpdivoPhase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin
IpilimumabYervoyPhase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin
LurbinectedinPhase 1 Dose Level 1: Nivolumab and Ipilimumab plus Lurbinectedin

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose Level 1: Nivolumab and Ipilimumab plus LurbinectedinExperimentalParticipants 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.
  • Nivolumab
  • Ipilimumab
  • Lurbinectedin
Phase 1 Dose Level 2: Nivolumab and Ipilimumab plus LurbinectedinExperimentalParticipants 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.
  • Nivolumab
  • Ipilimumab
  • Lurbinectedin
Phase 1 Dose Level 3: Nivolumab and Ipilimumab plus LurbinectedinExperimentalParticipants 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.
  • Nivolumab
  • Ipilimumab
  • Lurbinectedin
Phase 2: Treatment at Maximum Tolerated DoseExperimentalParticipants will be treated with nivolumab 1mg/kg, ipilimumab 3mg/kg plus maximum tolerated dose of 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 MTD every 3 weeks.
  • Nivolumab
  • Ipilimumab
  • Lurbinectedin

Eligibility 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:

        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:

               1. History or presence of unstable angina, myocardial infarction, congestive heart
                  failure, or clinically significant valvular heart disease within last year.

               2. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing
                  treatment.

               3. 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.

               4. 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.

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active
             Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is
             detected).

          -  Has received a live vaccine within 30 days of start of study therapy. Note: Seasonal
             influenza vaccines for injection are generally inactivated flu vaccines and are
             allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated
             vaccines, and are not allowed.

          -  Patients who had a prior Grade ≥3 immune-related adverse event (e.g. pneumonitis,
             hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine,
             cytokine, etc.).

          -  Patients must not be pregnant or nursing due to risk of fetal or nursing infant harm.
             WOCBP must have agreed to use an effective contraceptive method.

          -  Participants with interstitial lung disease that is symptomatic or may interfere with
             the detection or management of suspected drug-related pulmonary toxicity.

          -  Participants who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Maximum Tolerated Dose (MTD) of Lurbinectedin with Nivolumab and Ipilimumab
Time Frame:Up to 12 weeks per cohort
Safety Issue:
Description:Maximum tolerated Dose will be determined by testing increasing doses of Lurbinectedin along with fixed doses of Nivolumab and Ipilimumab.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.
Measure:Progression Free Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last clinical follow-up date.
Measure:Overall Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Survival is defined as the time from study enrollment to death from any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Last Updated

March 3, 2021