Lurbinectedin With Osimertinib in Transformed Small Cell Lung Cancer

NCT07153055 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CTO-IUSCCC-0891
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, Phase I/II trial is studying the safety and effectiveness of an experimental drug combination, lurbinectedin with osimertinib, against a rare type of cancer known as transformed small cell lung cancer (SCLC).

Conditions

Small Cell Lung Cancer ( SCLC ); Transformed Small Cell Lung Cancer

Keywords

EGFR mutations

Outcome Measures

Primary Outcomes (1)

• Grade 3 or dose-limiting toxicities

  The number of incidences of grade 3 or dose-limiting toxicities of the combination of lurbinectedin with osimertinib assessed using NCI CTCAE v5.0 criteria.

  Within 30 days after your last dose of study treatment.

Secondary Outcomes (1)

• Progression-free survival

  Within 30 days after your last dose of study treatment.

Study Arms (2)

Phase I Does De-Escalation

EXPERIMENTAL

3.2 mg/m2 or 2.6 mg/m2 dose of lurbinectedin with 80 mg or 40 mg daily dose of osimertinib. This will occur day 1 of each 21 day cycle.

Drug: Lurbinectedin; Drug: Osimertinib

Phase II Dose Expansion

EXPERIMENTAL

3.2 mg/m2 or 2.6 mg/m2 dose of lurbinectedin with 80 mg or 40 mg daily dose of osimertinib. This will occur day 1 of each 21 day cycle.

Drug: Lurbinectedin; Drug: Osimertinib

Interventions

Lurbinectedin DRUG

Two lurbinectedin does of 3.2 mg/m2 or 2.6 mg/m2. The initial starting dose is 3.2 mg/m2. Patients will receive lurbinectedin, until disease progression or unacceptable toxicity, once every 21 days.

Phase I Does De-Escalation; Phase II Dose Expansion

Osimertinib DRUG

Two osimertinib does of 80 mg or 40 mg orally once daily, as assigned by the dose de-escalation cohort for each 21 day cycle.

Phase I Does De-Escalation; Phase II Dose Expansion

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years old at the time of informed consent.
• Ability to provide written informed consent and HIPAA authorization.
• Must have a histologically or cytologically confirmed transformation to small cell lung carcinoma/cancer.
• Must have an initial diagnosis of EGFR altered (EGFR-mutated) non-small cell lung cancer and received EGFR targeted therapy (TKI) osimertinib, and does not demonstrate evidence of acquired molecular underpinnings (i.e., presence of a MET amplification \>6 copies or EGFR C797S) resulting in progression on osimertinib, aside from histologic transformation to small cell lung cancer. Interruptions of osimertinib prior to enrollment on study is permitted.
• Note: Tissue specimens from archival tissue are encouraged but not required for enrollment.
• Patients who have received platinum (cisplatin or carboplatin)/etoposide after histologic transformation are permitted on study. Receipt of last cycle of therapy should be at least 3 weeks prior to initiation of treatment on study. Last exposure to immunotherapy such as anti-PD-L1 should be at least four weeks from treatment to initiation of treatment on study. Patients who decline to receive platinum/etoposide after SCLC transformation, for personal preferences or considered medical ineligible for this regimen, may be considered for this study, subject to investigator discretion.
• Must have measurable disease per RECIST (version 1.1).
• ECOG performance status ≤ 2.
• Adequate laboratory functions on baseline testing within 21 days of enrollment, as defined as:
• a. Hematologic parameters: i. Absolute neutrophil count (ANC) ≥ 1.5x109/L ii. Platelet count (Plt) ≥ 100x109/L b. Hepatic parameters: i. Total bilirubin ≤ 1.5x upper limit of normal (ULN); for patients with suspected/documented Gilbert's syndrome, total bilirubin ≤ 3x ULN.
• ii. AST ≤ 3x ULN. iii. ALT ≤ 3x ULN. c. Renal parameters: i. Creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR, calculated per institutional standards) should be \> 30 mL/min.
• Women of childbearing potential must have a negative pregnancy test within 21 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:
• i. Has achieved menarche at some point; or ii. Has not undergone a hysterectomy or bilateral oophorectomy; or iii. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Women of childbearing potential and men with any partners of child-bearing potential must agree to use 2 forms of effective contraception throughout the study and for 6 months after the last study treatment.
• Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections).

You may not qualify if:

• Patients who have tumors harboring EGFR exon 20 insertion alterations, EGFR C797S, or known mechanisms of resistance to osimertinib (i.e., MET amplification) aside from histologic transformation to SCLC.
• Patients who are pregnant (treatment can cause fetal harm) and/or breastfeeding.
• Symptomatic or unstable brain metastases, requiring \> 2 mg dexamethasone orally daily, or received palliative radiation to the CNS within 2 weeks of enrollment.
• Patients with known history of interstitial lung disease (ILD) or pneumonitis (\> grade 1) or ILD/pneumonitis (\> grade 1) related to antineoplastic drug treatment.
• Prior history of documented Stephen Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), erythema multiforme major (EMM), or aplastic anemia on osimertinib.
• History of congenital long QTc syndrome or mean resting QTc \>500 msec at screening with two replicated EKGs at baseline screening for the study.
• History of ongoing unstable or uncontrolled cardiac conditions, including documented cardiomyopathy or symptomatic congestive heart failure (defined as New York Heart Association (NYHA) class III or IV).
• Prior history of documented severe allergic or anaphylactic reaction to osimertinib.
• Prior history of documented aplastic anemia with osimertinib.
• Prior history of documented allergic or anaphylactic reactions to inactive ingredients of lurbinectedin, including sucrose, lactic acid, and sodium hydroxide.

Sponsors & Collaborators

• Misty Shields: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

PM 01183; osimertinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Misty D Shields, MD, PhD

  Indiana University Melvin and Bren Simon Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lori Tyson, RN

CONTACT

317-274-0895; lotyson@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Adjunct Assistant Professor of Medical & Molecular Genetics

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 3, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (1)