Study of NMS-03305293 in Adult Patient With Relapsed Small Cell Lung Cancer

NCT06931626 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PARPA-293-004
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label study of NMS-03305293 with Temozolomide (TMZ) in patients with Small Cell Lung Cancer (SCLC). The aim of this study is to determine the safety and tolerability, as well as to evaluate the anti-tumor efficacy and pharmacokinetics of NMS-03305293 in combination with TMZ.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events (AEs)

  Evaluation of type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 5.0), duration of AEs, electrocardiogram (ECG) and laboratory abnormalities

  Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 12 months)

Secondary Outcomes (16)

• Overall Response Rate (ORR)

  From the date of first response up to data cut-off (approximately 12 months)

• Duration of response (DoR)

  From the date of first response up to data cut-off (approximately 12 months)

• Progression-free survival (PFS)

  From the date of treatment initiation up to data cut-off (approximately 12 months)

• Overall survival (OS)

  From the date of treatment initiation up to data cut-off (approximately 12 months)

• Maximum plasma concentration (Cmax) of NMS-03305293

  Cycle 1 - Day 1 and Day 5. Each cycle is 28 days

Study Arms (1)

NMS-03305293 and Temozolomide

EXPERIMENTAL

NMS-03305293 will be dosed orally on days 1-28 of each 28-day cycle, at 100 mg twice daily. Temozolomide will be dosed orally on days 1-5 of each 28-day cycle, at 150 mg/m\^2, based on patients' body surface area.

Drug: NMS-03305293; Drug: Temozolomide

Interventions

NMS-03305293 DRUG

Route of administration: Oral

NMS-03305293 and Temozolomide

Temozolomide DRUG

Route of administration: Oral Commercially available Temozolomide

NMS-03305293 and Temozolomide

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed extensive-stage Small Cell Lung Cancer (SCLC); must have failed prior front-line platinum-based therapy including immune therapy with relapse within 6 months followed by failed tarlatamab therapy, if available and appropriate, and no more than 3 total prior lines of systemic therapy (therapy terminated due to toxicity or drug shortage, in the absence of Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression, will be considered part of the same line). Sponsor may opt to allow history of treatment free interval from front-line longer than 6 months .
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient must have progressed radiographically on or after their most recent line of anticancer therapy and have measurable disease as defined by RECIST v1.1 (radiologically measured by the Investigator).
• The interval from prior antitumor treatment should be at least 2 weeks or 5 half-lives, whichever longer.
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 Grade ≤ 1 or to the baseline laboratory values as defined in the protocol.
• Patients must use highly effective contraception or true abstinence.
• Ability to swallow capsules intact (without chewing, crushing, or opening).

You may not qualify if:

• Current enrollment in another interventional clinical trial.
• Current treatment with other anticancer agents or devices.
• Major surgery, other than surgery for recurrent SCLC, within 4 weeks prior to treatment start.
• Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow.
• Histologically transformed SCLC, i.e. tumors initially diagnosed as Non-Small Cell Lung Cancer (NSCLC) or mixed lung adenocarcinoma
• Known paraneoplastic syndrome uncontrolled or that required therapeutic changes (either new/acute or chronic) in the 14 days prior to study entry
• Use of full-dose anticoagulants unless the International Normalized Ratio (INR) or a Partial Thromboplastin Time (PTT) is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks before enrollment.
• Treatment with concomitant medications known to be sensitive substrates of CYP2D6 and CYP2C19 that cannot be replaced with another treatment.
• Treatment with systemic immune modulators such as corticosteroids at prednisone equivalent dose of \> 10 mg/day, cyclosporine and tacrolimus or radiotherapy within 28 days before treatment start.
• Breast-feeding women or women planning to breast feed during the study or within 3 months after study treatment.
• Known hypersensitivity to any component of NMS-03305293 or Temozolomide (TMZ) drug formulations.
• Known active, life-threatening or clinically significant uncontrolled systemic infection (bacterial, fungal, viral including Human Immunodeficiency Virus \[HIV\] positivity or Hepatitis B Virus \[HBV\] or Hepatitis B Virus \[HCV\] infections) requiring systemic treatment; HIV or Acquired Immune Deficiency Syndrome (AIDS)-related illness are allowed as long as controlled more than 6 months to undetectable on anti-HIV medications.
• Patients with QT interval using Fridericia standard (QTcF) interval \>450 milliseconds or with risk factors for torsade de pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of prolonged QTc interval or family history of long QT syndrome). For patients receiving treatment with concomitant medications known to prolong the QTc interval, replacement with another treatment prior to enrollment is mandatory. If concomitant use of anti-emetics is considered essential for the care of the patients, follow instruction in this protocol
• Known active gastrointestinal disease (e.g., documented gastrointestinal ulcer, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes or structural issues or ulcer that would impact on drug absorption.
• Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, active bleeding disorder and interstitial lung disease.

Sponsors & Collaborators

• Nerviano Medical Sciences: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Domenico Roberti

CONTACT

+39 0331-581111; clinicaltrials@nervianoms.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2025
• First Posted: April 17, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

US (2)