Status:
NOT_YET_RECRUITING
Lurbinectedin With Osimertinib in Transformed Small Cell Lung Cancer
Lead Sponsor:
Misty Shields
Collaborating Sponsors:
Jazz Pharmaceuticals
Conditions:
Small Cell Lung Cancer ( SCLC )
Transformed Small Cell Lung Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
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...
Detailed Description
This is an open label prospective multicenter Phase Ib/II trial utilizing a Bayesian Optimal Interval (BOIN) dose-finding design to identify the maximum tolerated dose (MTD) based on DLTs of lurbinect...
Eligibility Criteria
Inclusion
- Inclusion Criteria
- ≥ 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).
- Male subjects must agree to refrain from donating sperm during the study and for 6 months after the last study treatment. Female subjects must agree to refrain from donating eggs during the study and for 6 months after the last study treatment.
- Exclusion Criteria
- 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.
Exclusion
Key Trial Info
Start Date :
May 1 2026
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 1 2029
Estimated Enrollment :
16 Patients enrolled
Trial Details
Trial ID
NCT07153055
Start Date
May 1 2026
End Date
October 1 2029
Last Update
December 18 2025
Active Locations (1)
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1
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States, 46202