Clinical Trials

IRB Study Number 20216736

Status Recruiting

Phase Phase 3

Locations Robert and Carol Weissman Cancer Center, Martin North Hospital

Institute Taussig Cancer Institute

Description

This is a Phase III, randomized, double-blind, multicenter, three arm, international study assessing the efficacy and safety of Durvalumab in combination with oleclumab or monalizumab in participants with locally advanced (Stage III), Unresectable NSCLC with WHO performance status of 0 or 1, who have not progressed on definitive, platinum-based cCRT.

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Inclusion Criteria

In order to expedite tissue analysis, part I screening procedures may begin before cCRT has been completed.

1. Participant must be ≥ 18 years at the time of screening.
2. Participants must have histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease.
3. Tumor sample requirements as follows: Provision of a tumor tissue sample (obtained ≤ 3 months prior to Screening is preferred; ≤ 6 months prior to Screening is acceptable). The tumor sample must be obtained prior to CRT.
4. Documented tumor PD-L1 status as determined by a central laboratory testing assay prior to randomization. Patients with unknown PD-L1 status are not eligible for study.
5. Documented EGFR and ALK wild-type status.
6. Capable of giving signed informed consent for tumor sample collection that includes compliance with the requirements and restrictions listed in the pre-screening informed consent form (part I screening ICF).

Part II Screening procedures - Participants are eligible to be randomized to the study only if all of the following Part II inclusion criteria and none of the exclusion criteria apply:

1. Patients must not have progressed following definitive, platinum-based, cCRT as demonstrated by the following imaging studies performed after completion of CRT.
2. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy, which must be completed within 1 to 42 days prior to first dose of investigational product in the study.
3. The platinum-based chemotherapy regimen must be cisplatin or carboplatin-based and contain one of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local standard of care regimens. Gemcitabine is not permitted.
4. The last dose of chemotherapy must be administered prior to, or concurrently with, the final dose of radiation. Consolidation chemotherapy after radiation is not permitted. Up to 2 cycles of induction chemotherapy prior to cCRT is permitted.
5. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomized. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
6. Minimum body weight ≥ 40 kg at enrolment and randomization.
7. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

1. As judged by the investigator, any evidence of diseases chronic diverticulitis or previous complicated diverticulitis which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease > 5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumors without evidence of disease.
3. Mixed small cell and non-small cell lung cancer histology.
4. Participants who have had disease considered for surgical treatment as part of their care plan.
5. Participants with T4 lesions that invade major vascular structures such as pulmonary artery or cardiac tissues are not eligible.
6. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
7. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
8. Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
9. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis – regardless of time of onset prior to randomization.
10. Active or prior documented autoimmune or inflammatory disorders.
11. History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia.
12. Participation in another clinical study with a study intervention during the last 3 months prior to randomization or concurrent enrolment in another clinical study, unless it is and observational, non-interventional clinical study during the follow-up period of an interventional study.