Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)

NCT05035745 | Recruiting Phase 1

• 1 other identifier: MC01/05/20; IST-325 (KPT)
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.

Conditions

Advanced Refractory Solid Tumors; Advanced Triple Negative Breast Cancers; Metastatic Triple Negative Breast Cancers

Keywords

Selinexor; Talazoparib; breast cancer; Triple negative

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Study Arms (1)

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.

Drug: Talazoparib; Drug: Selinexor

Interventions

Talazoparib DRUG

Patients will be treated with Talazoparib daily on a 4 weekly cycle (28 days)

Patients with refractory solid tumors

Selinexor DRUG

Patients will be treated with Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days)

Patients with refractory solid tumors

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• b) 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (2)

• 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.

  PMID: 30345906 BACKGROUND

• Robson 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.

  PMID: 30689707 BACKGROUND

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

talazoparib; selinexor

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Soo Chin Lee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Chin Lee

CONTACT

6779 5555; soo_chin_lee@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: September 5, 2021
• Study Start: March 1, 2021
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)