Iadademstat in Combination With Paclitaxel in Relapsed/Refractory SCLC and Extrapulmonary High Grade NET

NCT05420636 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: GI-203
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This is a non-randomized single-arm, two cohorts, phase II study of iadademstat in combination with weekly paclitaxel in patients with relapse/refractory SCLC or extrapulmonary G3 Neuroendocrine Carcinomas. A total of 42 patients with SCLC (21 patients) and G3 NEC (21 patients) will be enrolled (including those enrolled in the safety lead-in portion).

Conditions

Small-cell Lung Cancer; Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy in terms of response rate of iadademstat combination with paclitaxel in relapsed/refractory SCLC and extrapulmonary high grade neuroendocrine cancers. Assessments will be performed after every 2 cycles of treatments.

  To determine Overall response rate (ORR) per RECIST1.1 ORR is defined as patients who meet criteria for Complete Response (CR) or Partial response (PR).

  2 years

Secondary Outcomes (2)

• To determine the Rate of grade III or higher toxicities

  2 years

• Progression free survival (PFS), defined as the time from initiation of study drug until documented radiographic progression, clinical progression, death, or the end of follow-up, whichever occurs first.

  2 years

Study Arms (1)

Iadademstat plus Paclitaxel

EXPERIMENTAL

Iadademstat oralon a 5 day ON and 2-day OFF schedule every week plus Paclitaxel administered intravenously weekly on day 1, 8 and 15 on day 1 of a 21 day treatment cycle.

Drug: Iadademstat; Drug: Paclitaxel

Interventions

Iadademstat DRUG

Patients will be treated with iadademstat given at a dose of 150 microgram PO administered on a 5 day on-2 day off schedule every week (days 1 through 21)

Iadademstat plus Paclitaxel

Paclitaxel DRUG

Patients will be treated with Paclitaxel given at a dose of 80 mg/m2 intravenous administration weekly day 1, 8 and 15 (days 1 through 21).

Iadademstat plus Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic or unresectable, extrapulmonary G3 NEC (Ki-67 index \> 20% with poorly-differentiated histology), SCLC, or prostate or bladder cancer with high-grade neuroendocrine or small cell component
• Patients must have been previously treated with platinum-based chemotherapy regimens (cisplatin, carboplatin or oxaliplatin). Patients may have received up to 3 lines of treatment in the metastatic setting that might include immune checkpoint inhibitors, but no previous taxane based therapy. However, patients who have received neoadjuvant/adjuvant therapy with taxanes more than six months from enrollment are allowed to participate.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 11.0
• Patients who have received prior anti-PD1 or anti-PD-L1 therapy are eligible to enroll 5 Age \> 18 years. 6 ECOG performance status 0-1 7 Body weight \>/= 50 kg (110 lbs) 8 Patients must have normal organ and marrow function as defined below
• Absolute neutrophil count \> 1,500/mcL
• Hemoglobin \> 9 mg/dl
• Platelets \> 100,000/mcL (patients cannot receive platelet transfusions to meet eligibility criteria)
• Total bilirubin \< 1.5 X ULN (Pts with Gilbert's can enroll if conjugated bilirubin is within normal limits)
• AST/ALT (SGOT/SGPT) \< 3 x ULN if not disease related. If liver metastasis, AST/ALT up to 5 x ULN allowed.
• Creatinine \<1.5 X ULN OR
• Creatinine clearance \> 60 ml/min/1.73 m2 for patients
• Patient is able to swallow oral medications and retain orally administered study treatment.
• Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document.
• HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. Similarly, Hepatitis B and C infected patients are allowed if disease is controlled (testing not required for eligibility assessment) 13 Male patients even if surgically sterilized (i.e., status post-vasectomy) who agree to:

You may not qualify if:

• Patients who have received more than 3 lines of therapy
• Patients who have not received any platinum-based therapy
• Patients who have received previous therapy with taxanes, unless received in the neoadjuvant/adjuvant setting and longer than six months from last taxane treatment.
• ECOG performance status \>/=2
• 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 as per treating MD
• Patients who have received radiotherapy less than 2 weeks prior to first dose of study medication.
• Surgical procedure or clinically significant trauma within 4 weeks of first dose of study treatment.
• Treatment with any investigational agent ≤ 3 weeks prior to first dose of study treatment.
• Patients with gastrectomy or pre-existing gastrointestinal (GI) disorders that may interfere with the proper absorption of the drug(s), as per conclusion of the clinical Investigator.
• Patients medicated with, or the expected need for treatment with agents reported to have LSD1 inhibitory activity (such as tranylcypromine or phenelzine) within 3 weeks of treatment start also refer to section 5.2 for the list of concomitant medications.
• History of allergic reactions attributed to components of the formulated product(s). (see appendix)
• Patients with prior history of NCI CTCAE Grade ≥ 3 drug-related central nervous system (CNS) toxicity.
• Patients with untreated, symptomatic CNS metastases likely to interfere with the experimental therapy as per the investigator-sponsor
• Patients with prior history of grade ≥2 neurotoxicity that was not resolved to grade ≤1 (prior therapy toxicity)
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study or pose a higher risk of toxicities as per discretion of the treating physician in agreement with the investigator-sponsor (including but not limited to:)

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Oryzon Genomics S.A.: collaborator

Study Sites (3)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine

Interventions

iadademstat; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Namrata Vijavergia

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 15, 2022
• Study Start: December 21, 2022
• Primary Completion: July 23, 2025
• Study Completion: July 23, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-07

Locations

US (3)