Eligible participants with limited stage-small cell lung cancer (LS-SCLC) will be enrolled after completion of chemotherapy and radiation. Participants will be randomized to either tarlatamab in combination with durvalumab or durvalumab alone as consolidation therapy. Treatment will continue until disease progression, unacceptable side effects or withdrawal of consent. Tarlatamab is a targeted cancer treatment. It works by acting as a matchmaker between the immune system's T-cells and the cancer cells, forcing them to come together so the T-cells can attack the cancer. Image testing will be done standardly during treatment. These tests show whether the cancer has progressed and if further treatment may be needed. The purpose of this trial is to evaluate how well the treatment works (how long before your cancer comes back and how long you live).
The purpose of this trial is to evaluate the clinical efficacy of tarlatamab in combination with durvalumab as consolidation therapy for LS-SCLC after completion of chemotherapy and radiation compared to durvalumab alone. Tarlatamab has demonstrated significant clinical activity against SCLC in the extensive stage setting and demonstrated improved overall survival compared to second line chemotherapy. The durability of response and progression-free survival (PFS) rates are encouraging that this therapy has the ability to achieve more long-term disease control than traditional treatments like chemotherapy and programmed cell death-ligand 1 (PD-L1) immunotherapy alone. Given the high risk of recurrence and death for LS-SCLC, tarlatamab may be an effective strategy to improve the risk of recurrence and death in this earlier disease setting. Tarlatamab is a bi-specific T-cell engager that targets delta-like ligand 3 (DLL3) and CD3 and was developed with the intent to treat small cell lung cancer due to the high level of expression of DLL3 on the cell surface. The anti-tumor activity of tarlatamab requires simultaneous binding to both target cells and T cells. RECIST 1.1 criteria will be used for disease response. This is will be measured by the investigators as well as a Blinded Independent Central Review (BICR). Archived tumor tissue will be requested at baseline for future research. Research peripheral blood samples will be obtained to measure the level of tarlatamab and for future research. Patient-reported outcomes will also be performed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
430
Tarlatamab Intravenous (IV): Cycle 1 Step Dose: Day 1- 1 mg; Day 8- 10 mg; Day 15- 10 mg of a 28-day cycle, then Cycle 2 and Subsequent Cycles: Day 1- 10 mg and Day 15- 10 mg every 28-day cycle up to 12 months from cycle 1 day 1 unless other treatment discontinuation or rechallenge criteria are met.
Durvalumab 1500 mg IV: Every 4 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months from cycle 1 day 1, unless other treatment discontinuation criteria are met.
This phase III study has dual primary endpoints of progression-free survival (PFS) and overall survival (OS).
The dual primary endpoints are PFS by Blinded Independent Central Review (BICR) and OS. OS is defined as time from randomization until death due to any cause.
Time frame: From randomization until death due to any cause, assessed up to 131 months.
This phase III study has dual primary endpoints of progression-free survival (PFS) and overall survival (OS).
The dual primary endpoints are PFS by Blinded Independent Central Review (BICR) and OS. PFS is defined as the time from randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first, in the absence of subsequent anticancer therapy. For participants with post-baseline imaging assessments, PFS will be censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy or the earlier of the following, where applicable: (a) the last evaluable post-baseline tumor assessment prior to or on subsequent anticancer therapy, or (b) the last post-baseline assessment that precedes two or more consecutive missing/not evaluable assessments followed by disease progression or death. For participants with no post-baseline imaging assessments, PFS will be censored at the date of randomization.
Time frame: From randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first, assessed up to 131 months.
Secondary endpoints include safety/tolerability.
Toxicity will be determined using the CTCAE V6.0. Toxicity will be assessed by summaries by CTCAE grade. Participants will be followed for adverse events for 90 (+5) days after their last dose of study medication. However, if a participant experiences an adverse event \>90 (+5) days after their last dose of study medication that is felt to be, in the opinion of the investigator, possibly, probably or definitely related to study therapy, the adverse event should be reported.
Time frame: From treatment start to 90 (+5) days after their last dose of study medication.
Secondary endpoints include investigator-assessed PFS.
Secondary objectives include to evaluate the difference in investigator-assessed PFS per RECIST 1.1 with tarlatamab + durvalumab as compared to durvalumab alone.
Time frame: From randomization until the first documentation of investigator-assessed radiologic disease progression or death due to any cause, whichever occurs first, assessed up to 131 months.
Secondary endpoints 3 and 5-year PFS rate
3 and 5-year PFS is defined as the Kaplan-Meier-estimated probabilities of being alive and progression-free at 3 years and 5 years.
Time frame: From randomization to 3 and 5 years after randomization.
Secondary endpoints include 3 and 5-year OS rate.
3 and 5-year OS is defined as the Kaplan-Meier-estimated probabilities of being alive at 3 years and 5 years.
Time frame: From randomization to 3 and 5 years after randomization.
Secondary endpoints include cumulative incidence Central Nervous System (CNS) metastases.
The BICR will conduct 2 assessments of tumor response using RECIST 1.1: one for the overall systemic disease (based on non-target and new lesions) and one solely for the evaluation of CNS endpoints (based on brain metastases only).
Time frame: From randomization until last follow-up, assessed up to 131 months.
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