Iadademstat + SBRT With Atezo in ES-SCLC

NCT07113691 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2000039106
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Keywords

persistent, recurrent or progressive disease after first line systemic therapy

Outcome Measures

Primary Outcomes (6)

• 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.

  35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long

• 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.

  35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long

• 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.

  35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long

• 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.

  35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long

• Rate of Adverse Events (AEs) in patients treated with iadademstat combined with atezolizumab and SBRT

  The proportion of participants experiencing adverse events (AEs), expressed as a percentage of the total participants, will be calculated. This measure aims to quantify the incidence rate of AEs in patients treated with iadademstat combined with atezolizumab and SBRT.

  35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long

• Grade of Adverse Events (AEs) in patients treated with iadademstat combined with atezolizumab and SBRT

  The severity of adverse events (AEs) 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 AEs experienced by the participants.

  35 days post the first dose of study drug on Cycle 1 Day 1, each cycle is 28 days long

Secondary Outcomes (6)

• Disease control rate in patients treated with iadademstat combined with atezolizumab and SBRT

  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 treatment

• Objective response rate in patients treated with iadademstat combined with atezolizumab and SBRT

  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 treatment

• Duration of response in patients treated with iadademstat combined with atezolizumab and SBRT

  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 years

• Progression free survival in patients treated with iadademstat combined with atezolizumab and SBRT

  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 years

• Overall Survival (OS) in patients treated with iadademstat combined with atezolizumab and SBRT

  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 years

Study Arms (1)

Iadademstat + Atezolizumab

EXPERIMENTAL

The first three participants will start iadademstat at a dose of 600ug PO weekly (DL 1). Dose escalation and de-escalation will be guided by the BOIN design. Dose finding will continue until the pre-specified sample size of 15 is reached or stop the trial if the number of participants treated at the current dose reaches 12 and the decision is to stay at the current dose. Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1680mg on Day 1 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 (e.g., symptomatic deterioration such as pain secondary to disease).

Drug: Iadademstat; Drug: Atezolizumab; Radiation: SBRT

Interventions

Iadademstat DRUG

Iadademstat 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.

Iadademstat + Atezolizumab

Atezolizumab DRUG

Atezolizumab 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.

Iadademstat + Atezolizumab

SBRT RADIATION

The 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

Iadademstat + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Histologically documented ES-SCLC previously treated with at least one regimen, including a platinum containing chemotherapy regimen, with progression of disease on or after their most recent therapy or achieving only SD after completion of one line of a platinum containing chemotherapy-based regimen.
• a. Participants previously diagnosed with limited stage SCLC treated with concurrent chemoradiation with a platinum doublet now diagnosed with recurrent extensive disease in the relapsed setting are eligible.
• Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, antiPD-1, and anti-PD-L1 therapeutic antibodies is allowed.
• ECOG performance status of 0 to 2.
• At least one identified tumor lesion to be treated with SBRT.
• At least one additional tumor lesion, separate from the site of SBRT, preferably outside of the 5Gy isodose line, amenable to incisional, excisional, core or forceps (transbronchial) biopsy. Participants must be willing to undergo tumor biopsies before starting trial therapy and 2 weeks (+/- 1 week) after the completion of SBRT.
• If the initial biopsy is excisional, the excised tumor cannot be counted as a biopsy target lesion and there must be another lesion amenable to incisional, excisional, core or forceps biopsy. In this scenario, the second biopsy can only be excisional if the lesion to be excised is not a target lesion.
• Cytology tumor specimens (e.g., from fine-needle biopsies, or drainage of pleural/ pericardial or ascites fluid) are not acceptable. Biopsies of bone lesions that do not have a soft tissue component are also not acceptable (i.e., decalcified tumor samples are not acceptable). Non-lymph node sites will be biopsied preferentially.
• If enrolled with stable, but not progressive, disease at the completion of first line platinum-based therapy regimen, participants may undergo biopsy of the same site that is to be irradiated. If a separate site is identified for biopsy, it should be preferentially biopsied over the site that is to be irradiated.
• Participants must agree to submit blood samples for exploratory biomarker research at the times identified in the study calendar.
• Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can be counted as target lesions if clearly progressing after radiation.

You may not qualify if:

• History of leptomeningeal disease.
• Untreated symptomatic CNS metastases. Participants with asymptomatic CNS metastases are eligible. Participant with treated symptomatic brain metastases is eligible provided they meet all of the following criteria:
• 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.
• The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for more than or equal to 1 week prior to enrollment.
• Uncontrolled tumor-related pain.
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Participants should be recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• a. Participants with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium greater than 1.5 mmol/L, calcium greater than 12 mg/dL or corrected serum calcium greater than ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix 1. Preexisting Autoimmune Diseases and Immune Deficiencies for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
• Participants with a history of autoimmune related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.

Sponsors & Collaborators

• Yale University: lead
• Genentech, Inc.: collaborator
• Oryzon Genomics S.A.: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

iadademstat; atezolizumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Annie Chiang, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carole Ramm

CONTACT

203-737-5801; carole.ramm@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 11, 2025
• Study Start: January 20, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)