Advanced Refractory Solid TumorsPhase 1/2NCT05035745
Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)
A Phase 1/2 study testing Talazoparib and Selinexor in people with Advanced Refractory Solid Tumors and Advanced Triple Negative Breast Cancers, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
This is a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Advanced Refractory Solid Tumors, Advanced Triple Negative Breast Cancers, Metastatic Triple Negative Breast Cancers
- What is being tested?
- Talazoparib and Selinexor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Mar 2021to Nov 2027
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must sign an informed consent in accordance with local institutional guidelines.
- All patient must not have received prior PARPi including talazoparib
- All patients must not have prior therapy with selinexor.
- Age ≥ 18
- Estimated life expectancy of at least 12 weeks.
- Has recovered from acute toxicities from prior anti-cancer therapies to grade 2 or lower.
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- a) Dose escalation phase: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry that is deemed unlikely to benefit from further conventional therapy, or for which no standard therapy is available.
- Dose expansion phase: Patients with previously treated, advanced or metastatic histologically or cytologically confirmed triple negative breast cancers. Patients must have evidence of progressive disease on study entry after at least one line of anti-cancer therapy. Patients will be stratified into platinum-naïve (not having been treated with platinums-containing chemotherapy in the neoadjuvant, adjuvant or palliative setting), platinum sensitive (defined as having prior objective response or sustained disease control lasting ≥6 months to platinum-containing chemotherapy in the metastatic setting, or relapsed ≥6 months after completing neoadjuvant or adjuvant platinums-containing chemotherapy), and platinum resistant (defined as having progressive disease as the best response or disease control <6 months to platinum-containing chemotherapy in the metastatic setting, or relapsed <6 months after completing neoadjuvant or adjuvant platinums-containing chemotherapy).
- There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met. Hormone ablation therapy is considered an anti-cancer regimen. Radiation and surgery are not considered anti-cancer regimens.
- Measurable disease by RECIST 1.1 criteria.
- Eastern cooperative Oncology Group (ECOG) Performance Status of 0-1
- Adequate bone marrow function and organ function within 2 weeks of study treatment
- Adequate hematologic function defined as:
- Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 125 x 109/L during dose escalation phase; platelets ≥ 100 x 109/L during dose expansion phase
- Hemoglobin ≥ 9 x 109/L
- Hepatic function:
- Bilirubin ≤ 1.5 times the upper limit of normal (ULN)
- ALT or AST ≤ 2.5 times ULN (or ≤ 5 times ULN with liver metastases)
- Adequate renal function:
- Calculated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/(72 x creatinine mg/dL); multiply by 0.85 if female.
- Able to swallow tablets/ pills.
- Able to comply with study-related procedures.
- Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for 7 months following the last dose of study treatment
Who cannot join
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
- Major surgery within 28 days of study drug administration
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Pregnancy
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- Breast feeding
- Poorly controlled diabetes mellitus
- Second primary malignancy that is clinically detectable at the time of consideration for study enrolment (for phase II only).
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
- Unable to comply with study procedures
- Current or anticipated use of strong P-gp inhibitors: amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, verapamil
- Current or anticipated use of strong BCRP inhibitors: curcumin, cyclosporine A, eltrombopag, elacridar, fumitremorgin C, novobiocin, sulfasalazine
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore
Dr
About this study
Official title: Phase I Dose Finding Study of Selinexor and Talazoparib in Patients With Advanced Refractory Solid Tumors, Followed by Phase II Expansion Cohort Study in Patients With Advanced/ Metastatic Triple Negative Breast Cancers. (START)
This is a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.
Read the detailed description
Hypothesis The investigators hypothesize that the combination of Talazoparib and Selinexor will have clinical efficacy in TNBC, independent of BRCA mutation status.
Primary Objectives
- To determine the safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors.
- To determine the RP2D of Talazoparib and Selinexor combination therapy in patients with advanced/ metastatic solid tumors.
Secondary Objectives
- To determine the objective response rate to combination Talazoparib and Selinexor in advanced/ metastatic TNBCs.
Exploratory Objectives
- To assess the effect of the combination on pharmacokinetics of Talazoparib and Selinexor
- To explore the impact of pharmacogenetics on toxicity and efficacy of combination Talazoparib and Selinexor.
- To assess changes in circulating tumor cells and plasma biomarkers during treatment.
- To assess pharmacodynamic changes and predictive biomarkers in tumor tissue during treatment.
- Conditions
- Advanced Refractory Solid Tumors, Advanced Triple Negative Breast Cancers, Metastatic Triple Negative Breast Cancers
- Being tested
- Talazoparib, Selinexor
- Keywords
- Selinexor, Talazoparib, breast cancer, Triple negative
- Medical subject headings
- Triple Negative Breast Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TalazoparibDrug
Patients will be treated with Talazoparib daily on a 4 weekly cycle (28 days)
SelinexorDrug
Patients will be treated with Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days)
| Study group | Role | What they receive |
|---|---|---|
| Patients with refractory solid tumors | Experimental | Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of patients with refractory solid tumors to determine the RP2D. Receives: Drug: Talazoparib; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0.
Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final Safety evaluations will be performed for all patients prior to each cycle of treatment, and include taking a medical history, physical examination, adverse event documentation, full blood count, renal function, liver function tests and electrocardiogram (ECG).
Toxicities will be graded using the NCI CTCAE toxicity grading version 5.0.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start1 Mar 2021
- Primary completionNov 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Refractory Solid TumorsStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Sequential
- Model description
- Phase I Patients will be treated with Talazoparib daily and Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days) in a modified 3+3 dose escalation/ de-escalation design Phase II Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final objective response analysis, TNBC patients will be stratified into platinum-naïve/platinum sensitive versus platinum-resistant to determine if prior platinum sensitivity impacts objective response rates to the combination of Talazoparib and Selinexor.
- Masking
- None (open label)
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05035745
- Sponsor's protocol ID
- MC01/05/20; IST-325 (KPT)
- Status last verified
- Jul 2025
- First submitted
- 1 Mar 2021
- Last updated
- 25 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. doi: 10.1056/NEJMoa1809615. Epub 2018 Oct 20.
PubMed 30345906Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. doi: 10.1093/annonc/mdz012.
PubMed 30689707
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Finding Study of Selinexor and Talazoparib in Patients With Advanced Refractory Solid Tumors, Followed by Phase II Expansion Cohort Study in Patients With Advanced/ Metastatic Triple Negative Breast Cancers. (START)
- ClinicalTrials.gov ID
- NCT05035745
- Acronym / sponsor ID
- MC01/05/20; IST-325 (KPT)
- Conditions
- Advanced Refractory Solid Tumors, Advanced Triple Negative Breast Cancers, Metastatic Triple Negative Breast Cancers
- Keywords
- Selinexor, Talazoparib, breast cancer, Triple negative
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 5 Sep 2021 (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 a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.
Detailed description
Hypothesis The investigators hypothesize that the combination of Talazoparib and Selinexor will have clinical efficacy in TNBC, independent of BRCA mutation status.
Primary Objectives
- To determine the safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors.
- To determine the RP2D of Talazoparib and Selinexor combination therapy in patients with advanced/ metastatic solid tumors.
Secondary Objectives
- To determine the objective response rate to combination Talazoparib and Selinexor in advanced/ metastatic TNBCs.
Exploratory Objectives
- To assess the effect of the combination on pharmacokinetics of Talazoparib and Selinexor
- To explore the impact of pharmacogenetics on toxicity and efficacy of combination Talazoparib and Selinexor.
- To assess changes in circulating tumor cells and plasma biomarkers during treatment.
- To assess pharmacodynamic changes and predictive biomarkers in tumor tissue during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase I Patients will be treated with Talazoparib daily and Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days) in a modified 3+3 dose escalation/ de-escalation design Phase II Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final objective response analysis, TNBC patients will be stratified into platinum-naïve/platinum sensitive versus platinum-resistant to determine if prior platinum sensitivity impacts objective response rates to the combination of Talazoparib and Selinexor.
| Arm | Type | Receives |
|---|---|---|
| Patients with refractory solid tumors | Experimental | Drug: Talazoparib, Drug: SelinexorPhase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of patients with refractory solid tumors to determine the RP2D. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- All patients must sign an informed consent in accordance with local institutional guidelines.
- All patient must not have received prior PARPi including talazoparib
- All patients must not have prior therapy with selinexor.
- Age ≥ 18
- Estimated life expectancy of at least 12 weeks.
Key exclusion criteria (14 listed)
- Treatment within the last 30 days with any investigational drug.
- Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
- Major surgery within 28 days of study drug administration
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
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 |
|---|---|---|
| TalazoparibPatients will be treated with Talazoparib daily on a 4 weekly cycle (28 days) | Drug | Patients with refractory solid tumors |
| SelinexorPatients will be treated with Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days) | Drug | Patients with refractory solid tumors |
Primary outcome
safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0.
Time frame: 5 years
Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final Safety evaluations will be performed for all patients prior to each cycle of treatment, and include taking a medical history, physical examination, adverse event documentation, full blood count, renal function, liver function tests and electrocardiogram (ECG). Toxicities will be graded using the NCI CTCAE toxicity grading version 5.0.
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 25 Jul 2025.
- Results publication: PubMed 30345906Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. doi: 10.1056/NEJMoa1809615. Epub 2018 Oct 20.
- Results publication: PubMed 30689707Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. doi: 10.1093/annonc/mdz012.
- Individual participant dataSharing planned: No
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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.
Soo Chin Lee principal investigator
National University Hospital, Singapore
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 Talazoparib and Selinexor in people with Advanced Refractory Solid Tumors and Advanced Triple Negative Breast Cancers, run by National University Hospital, Singapore at 1 site in Singapore.
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 24 inclusion and 14 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 25 Jul 2025. 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 Singapore. 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 Soo Chin Lee (6779 5555, soo_chin_lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0. (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05035745, which also lists 2 linked publications.
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 25 Jul 2025.