Iadademstat + SBRT With Atezo in ES-SCLC
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorYale University
About this trial
This is a phase 1b dose escalation, open-label, non-randomized study of participants with residual, progressive or recurrent ES-SCLC who previously received platinum-based chemotherapy with or without immune checkpoint inhibitor therapy; participants who have achieved only stable disease at the completion of initial platinum-based treatment are eligible for enrollment.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Signed informed consent form.
Ability to comply with protocol, in the treating investigator's judgment.
Age 18 years or older.
Participant must have a body weight of at least 50 Kg.
Disqualifiers
History of leptomeningeal disease.
Completed stereotactic radiosurgery at least seven days prior to Cycle 1, Day 1 or completed whole brain radiation at least two weeks prior to Cycle 1, Day 1.
No evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy.
Ongoing steroid requirement of <10 mg of prednisone per day (or equivalent) as therapy for CNS disease; anticonvulsants are allowed.
Trial design
Design model
Single group
Treatments tested in this trial
Iadademstat
DrugIadademstat is administered orally (PO) on an empty stomach (two hours after eating or one hour prior to food ingestion). After drinking the entire solution, the participant will be asked to refill the bottle with water and drink it again. Then they will drink another glass of water to wash their mouth and esophagus. Time of administration of the drug should be the same every day, preferentially in the mornings, and the time should be registered using the Dosing Instructions and Participant Drug Diary. If a dose is missed, the dose should be administered as soon as possible within 24 hours of the missed dose time. If more than 24 hours have passed, or a dose is vomited, the participant should call their medical team for instructions.
Atezolizumab
DrugAtezolizumab will be administered by IV infusion at a fixed dose of 1680mg on Day 1 (+/-3 days) of each 28-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the treating investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Administration of atezolizumab will be performed in a monitored setting where there is immediate access to trained personnel and adequate equipment and medicine to manage potentially serious reactions.
SBRT
RadiationThe first fraction of SBRT should be delivered after the initiation of iadademstat and atezolizumab, ideally between Cycle 1, Day 8, and Cycle 1, Day 15. Initiation of SBRT may be delayed up to 14 days beyond Cycle 1, Day 15 if iadademstat dose adjustment is required for toxicity
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: Iadademstat + AtezolizumabExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Frequency of Dose-Limiting Toxicities (DLTs) in patients treated with iadademstat combined with atezolizumab and SBRT
The number of participants experiencing dose-limiting toxicities (DLTs) during the study period will be recorded, providing a measure of how frequently DLTs occur when iadademstat is combined with atezolizumab and SBRT.
Time frame
35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long2
Rate of Dose-Limiting Toxicities (DLTs) in patients treated with iadademstat combined with atezolizumab and SBRT
The proportion of participants experiencing dose-limiting toxicities (DLTs), expressed as a percentage of the total participants, will be calculated. This measure aims to quantify the incidence rate of DLTs in the study population.
Time frame
35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long3
Grade of Dose-Limiting Toxicities (DLTs) in patients treated with iadademstat combined with atezolizumab and SBRT
The severity of dose-limiting toxicities (DLTs) will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. This measure will help assess the clinical significance and impact of DLTs experienced by the participants.
Time frame
35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long4
Frequency of Adverse Events (AEs) in patients treated with iadademstat combined with atezolizumab and SBRT
The number of participants experiencing adverse events (AEs) of any kind, regardless of causality, during the study period will be recorded. This outcome measure will provide insight into the overall safety profile of the combination treatment.
Time frame
35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days longSecondary outcomes
1
Disease control rate in patients treated with iadademstat combined with atezolizumab and SBRT
Defined as the proportion of patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) for a minimum duration based on RECIST v1.1 criteria (or the specific criteria used). This measure will assess the efficacy of iadademstat in combination with atezolizumab and SBRT in controlling the disease.
Time frame
Measured at Cycle 2 Day 22, day 1 of subsequent cycles; where each cycle is 28 days long. Also at the survival follow up visit, which will occur 30 days post end of treatment2
Objective response rate in patients treated with iadademstat combined with atezolizumab and SBRT
Defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) based on RECIST v1.1 criteria. Tumor assessments will be conducted regularly during the study to determine the ORR for patients treated with the combination of iadademstat, atezolizumab, and SBRT.
Time frame
Measured at Cycle 2 Day 22, day 1 subsequent cycles; where each cycle is 28 days long. Also at the survival follow up visit, which will occur 30 days post end of treatment3
Duration of response in patients treated with iadademstat combined with atezolizumab and SBRT
The time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to four years4
Progression free survival in patients treated with iadademstat combined with atezolizumab and SBRT
This measure will evaluate the length of time during and after treatment that the patient lives without disease progression when treated with iadademstat, atezolizumab, and SBRT.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to four yearsSponsors and contacts
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Source ClinicalTrials.gov