Small Cell Lung Cancer ( SCLC )Phase 1/2LOTSNCT07153055
Lurbinectedin With Osimertinib in Transformed Small Cell Lung Cancer
A Phase 1/2 study testing Lurbinectedin and Osimertinib in people with Small Cell Lung Cancer ( SCLC ) and Transformed Small Cell Lung Cancer, run by Misty Shields at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer ( SCLC ), Transformed Small Cell Lung Cancer
- What is being tested?
- Lurbinectedin and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Oct 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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.
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- 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:
- 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.
- 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:
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
3172742556, greinerb@iu.edu
About this study
Official title: Phase I/II Trial of Lurbinectedin With Osimertinib in Transformed Small Cell Lung Cancer
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).
Read the 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 lurbinectedin and osimertinib. DLT period is 21 days beginning on C1D1. Once the MTD has been identified, 10 subjects total will be enrolled in a Phase II expansion. This number includes the 3 initial subjects in the corresponding MTD group. Subjects will receive a combination of lurbinectedin every 21 days and osimertinib daily, until progression or unacceptable toxicities.
- Being tested
- Lurbinectedin, Osimertinib
- Keywords
- EGFR mutations
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LurbinectedinDrug
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.
OsimertinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Lurbinectedin; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 30 days after your last dose of study treatment.
Secondary outcomes (1)
Progression-free survival
The average length of time of progression-free survival (PFS) of the combination of lurbinectedin with osimertinib.
Measured: Within 30 days after your last dose of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2025
- Study startJan 2027 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Cell Lung Cancer ( SCLC )Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Misty Shields
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Sponsor-investigator, Misty Shields, Indiana University
- Investigators
- Misty D Shields, MD, PhD, Principal investigator, Indiana University Melvin and Bren Simon Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07153055
- Sponsor's protocol ID
- CTO-IUSCCC-0891
- Acronym
- LOTS
- Status last verified
- Oct 2026
- First submitted
- 26 Aug 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Lurbinectedin With Osimertinib in Transformed Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT07153055
- Acronym / sponsor ID
- LOTS / CTO-IUSCCC-0891
- Keywords
- EGFR mutations
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Misty ShieldsUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- Jan 2027 (estimated)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 3 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 lurbinectedin and osimertinib. DLT period is 21 days beginning on C1D1. Once the MTD has been identified, 10 subjects total will be enrolled in a Phase II expansion. This number includes the 3 initial subjects in the corresponding MTD group. Subjects will receive a combination of lurbinectedin every 21 days and osimertinib daily, until progression or unacceptable toxicities.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I Does De-Escalation | Experimental | Drug: Lurbinectedin, Drug: Osimertinib3.2 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. |
| Phase II Dose Expansion | Experimental | Drug: Lurbinectedin, Drug: Osimertinib3.2 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- ≥ 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LurbinectedinTwo 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. | Drug | Phase I Does De-Escalation, Phase II Dose Expansion |
| OsimertinibTwo osimertinib does of 80 mg or 40 mg orally once daily, as assigned by the dose de-escalation cohort for each 21 day cycle. | Drug | Phase I Does De-Escalation, Phase II Dose Expansion |
Primary outcome
Grade 3 or dose-limiting toxicities
Time frame: Within 30 days after your last dose of study treatment.
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.
1 secondary outcome
Progression-free survival
Time frame: Within 30 days after your last dose of study treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Misty D Shields, MD, PhD principal investigator
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lurbinectedin and Osimertinib in people with Small Cell Lung Cancer ( SCLC ) and Transformed Small Cell Lung Cancer, run by Misty Shields at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lori Tyson, RN (317-274-0895, lotyson@iu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade 3 or dose-limiting toxicities (time frame: Within 30 days after your last dose of study treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.