Small Cell Lung CancerPhase 1NCT06931626
Study of NMS-03305293 in Adult Patient With Relapsed Small Cell Lung Cancer
A Phase 1 study testing NMS-03305293 and Temozolomide in people with Small Cell Lung Cancer, run by Nerviano Medical Sciences at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- NMS-03305293 and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Aug 2025to 28 Feb 2027
- Phase
- Phase 1
- 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
- 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 for small-molecule agents and chemotherapies. For prior biologic therapy, including monoclonal antibodies, antibody-drug conjugates, immune checkpoint inhibitors, and bispecific antibodies, the interval should be at least 4 weeks or 5 half-lives, whichever is longer, unless otherwise justified based on the agent's known pharmacokinetics, pharmacodynamics, and residual toxicities.
- 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).
Who cannot join
- 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
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- 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.
- History of long QT disorder or familial sudden death syndromes or related syndromes in the opinion of the Investigator.
- Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or cone biopsied or post curative intention in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
- Symptomatic, or untreated central nervous system (CNS) lesions except stable and well controlled with no neurological symptoms; patients receiving corticosteroids to control neurological symptoms should be on stable doses for at least 14 days before study entry.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
- NOTE: Other protocol defined inclusion and exclusion criteria may apply.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
- Recruiting
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
About this study
Official title: Study of NMS-03305293, a Non-Trapping PARP1-Specific PARP Inhibitor in Relapsed Small Cell Lung Cancer
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
- Being tested
- NMS-03305293, Temozolomide
- 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.
NMS-03305293Drug
Route of administration: Oral
TemozolomideDrug
Route of administration: Oral Commercially available Temozolomide
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: NMS-03305293; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 12 months)
Secondary outcomes (16)
Overall Response Rate (ORR)
Calculated as the proportion of evaluable patients who have achieved, as best overall response (BOR), complete response (CR) or partial response (PR) through Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Measured: From the date of first response up to data cut-off (approximately 12 months)
Duration of response (DoR)
Duration of response will be calculated from the date of either first CR or PR until the date of documented progression for patients who achieved CR or PR. Patients who died without report of progression will be considered non-events and censored at their last disease-free assessment date
Measured: From the date of first response up to data cut-off (approximately 12 months)
Progression-free survival (PFS)
Progression Free Survival will be calculated from the date of treatment initiation to the date of first documentation of disease progression, or death due to any cause, whichever occurs first
Measured: From the date of treatment initiation up to data cut-off (approximately 12 months)
Overall survival (OS)
Overall Survival will be calculated from the date of treatment initiation to the date of death due to any cause
Measured: From the date of treatment initiation up to data cut-off (approximately 12 months)
Maximum plasma concentration (Cmax) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Time to maximum plasma concentration (Tmax) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Area under the plasma concentration versus time curve up to the last detectable concentration (AUC) for NMS-03305293
Measured: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Minimum plasma concentration (Cmin) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Average plasma concentration (Cave) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Area under the plasma concentration versus time curve to infinity (AUCinf) for NMS-03305293
Measured: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Terminal elimination half-life (t1/2) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Oral plasma clearance (CL/F) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Apparent volume of distribution (Vd/F) of NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Accumulation ratio (Rac) of Cmax for NMS-03305293
Measured: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Rac of Area under the plasma concentration vs time curve within dosing interval (AUCdaily) for NMS-03305293
Measured: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Rac of Area under the plasma concentration up to the last detectable plasma concentration (AUClast) for NMS-03305293
Measured: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2025
- Study start15 Aug 2025
- Primary completion30 Oct 2026 (estimated)
- Study completion28 Feb 2027 (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 CancerStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nerviano Medical Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06931626
- Sponsor's protocol ID
- PARPA-293-004
- Status last verified
- Jul 2026
- First submitted
- 4 Apr 2025
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of NMS-03305293, a Non-Trapping PARP1-Specific PARP Inhibitor in Relapsed Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06931626
- Acronym / sponsor ID
- PARPA-293-004
- Conditions
- Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Nerviano Medical SciencesIndustry (pharma, biotech, devices)
- Study start
- 15 Aug 2025 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 17 Apr 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NMS-03305293 and Temozolomide | Experimental | Drug: NMS-03305293, Drug: TemozolomideNMS-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 for small-molecule agents and chemotherapies. For prior biologic therapy, including monoclonal antibodies, antibody-drug conjugates, immune checkpoint inhibitors, and bispecific antibodies, the interval should be at least 4 weeks or 5 half-lives, whichever is longer, unless otherwise justified based on the agent's known pharmacokinetics, pharmacodynamics, and residual toxicities.
- 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.
Key exclusion criteria (20 listed)
- 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
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 |
|---|---|---|
| NMS-03305293Route of administration: Oral | Drug | NMS-03305293 and Temozolomide |
| TemozolomideRoute of administration: Oral Commercially available Temozolomide | Drug | NMS-03305293 and Temozolomide |
Primary outcome
Number of Participants with Adverse Events (AEs)
Time frame: Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 12 months)
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
16 secondary outcomes
Overall Response Rate (ORR)
Time frame: From the date of first response up to data cut-off (approximately 12 months)
Duration of response (DoR)
Time frame: From the date of first response up to data cut-off (approximately 12 months)
Progression-free survival (PFS)
Time frame: From the date of treatment initiation up to data cut-off (approximately 12 months)
Overall survival (OS)
Time frame: From the date of treatment initiation up to data cut-off (approximately 12 months)
Maximum plasma concentration (Cmax) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Time to maximum plasma concentration (Tmax) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Area under the plasma concentration versus time curve up to the last detectable concentration (AUC) for NMS-03305293
Time frame: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Minimum plasma concentration (Cmin) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Average plasma concentration (Cave) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Area under the plasma concentration versus time curve to infinity (AUCinf) for NMS-03305293
Time frame: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Terminal elimination half-life (t1/2) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Oral plasma clearance (CL/F) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Apparent volume of distribution (Vd/F) of NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Accumulation ratio (Rac) of Cmax for NMS-03305293
Time frame: Cycle 1 - Day 1 and Day 5. Each cycle is 28 days
Rac of Area under the plasma concentration vs time curve within dosing interval (AUCdaily) for NMS-03305293
Time frame: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
Rac of Area under the plasma concentration up to the last detectable plasma concentration (AUClast) for NMS-03305293
Time frame: Cycle 1 - Days 1-2 and Days 5-6. Each cycle is 28 days
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 24 Jul 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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NMS-03305293 and Temozolomide in people with Small Cell Lung Cancer, run by Nerviano Medical Sciences at 3 sites 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 7 inclusion and 20 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 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 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.
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 Domenico Roberti (+39 0331-581111, clinicaltrials@nervianoms.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events (AEs) (time frame: Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 12 months)). 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 24 Jul 2026.