Status and phase
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About
The study treatment will consist of a platinum drug (carboplatin or cisplatin per investigator's choice) plus etoposide plus durvalumab plus monalizumab every 3 weeks for 4 cycles. After 4 cycles, subjects will continue maintenance treatment with durvalumab plus monalizumab every 4 weeks until disease progression, unacceptable toxicity, decision to stop study treatment, or withdrawal of consent. Patients who have received one prior cycle of treatment before enrolling on the study will receive a total of 4 cycles with monalizumab, durvalumab, and chemotherapy. There will be a safety lead-in phase, including 6 to 12 patients, to confirm the safety of the proposed dose of monalizumab to use in combination with chemotherapy and durvalumab.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Written informed consent and HIPAA authorization for release of personal health information prior to registration. Note: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status of 0-2.
Histologically or cytologically confirmed diagnosis of small cell lung cancer:
No prior systemic therapy for small-cell lung cancer, with the following exceptions:
--Up to one cycle of platinum doublet chemotherapy with or without durvalumab is allowed up to 4 weeks prior to registration on this study. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and monalizumab may be included only after consultation with the sponsor-investigator. Patients should not have received trilaciclib.
Measurable disease according to RECIST v1.1
Subjects with treated brain metastasis and those with untreated asymptomatic brain metastasis are eligible if they are clinically stable per investigator discretion and not requiring systemic steroids for ≥ 7 days. Prophylactic cranial radiation (PCI) is allowed per investigator's discretion.
Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to registration.
Females of childbearing potential must have a negative serum pregnancy test at screening.
Females of childbearing potential and male subjects must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception.
Life expectancy of ≥ 12 weeks.
Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable through PCR to be eligible for this trial. Testing is not required for screening unless mandated by local authorities. Local guidelines for testing should be followed.
Exclusion criteria
Body weight ≤ 40 kg.
Receipt of radiotherapy to the chest within 6 months prior to initiating systemic therapy or planned consolidation chest radiation therapy. NOTE: Radiation therapy outside of the chest for palliative care (e.g., bone metastasis) is allowed but must be completed before the first dose of the study medication.
Active infection requiring intravenous antibiotic therapy.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
History of active primary immunodeficiency.
Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
Presence of neurologic paraneoplastic syndrome.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., ulcerative colitis or Crohn's disease], systemic lupus erythematosus, sarcoidosis, Wegener syndrome [granulomatosis with polyangiitis], rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
Current or prior use of immunosuppressive medication within 7 days before the first dose of monalizumab and 'on-study' durvalumab. The following are exceptions to this criterion:
Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. NOTE: Subjects, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
Patients who have received prior one dose of durvalumab along with chemotherapy:
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per investigator discretion.
History of leptomeningeal carcinomatosis.
History of allogeneic organ transplantation.
Treatment with any investigational drug within 28 days prior to registration or concurrent enrolment in another clinical study, unless observational in nature.
Primary purpose
Allocation
Interventional model
Masking
38 participants in 1 patient group
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Central trial contact
Milena Petkov; Hirva Mamdani, MD
Data sourced from clinicaltrials.gov
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