Induction of Cisplatin/Nab-paclitaxel/Pembrolizumab Followed by Olaparib/Pembrolizumab Maintenance in mTNBC Patients

NCT05174832 | Unknown Phase 2 FDA Drug

• 1 other identifier: COMPLEMENT
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate if olaparib plus pembrolizumab will maintain the clinical benefit achieved after induction therapy with Albumin-bound paclitaxel combined with cisplatin(AP) regimen and pembrolizumab in previously untreated locally advanced, recurrent or metastatic TNBC population with PD-L1 CPS≥1.

Conditions

Triple Negative Breast Cancer

Keywords

Pembrolizumab; Olaparib; Platinum-based chemotherapy; Triple negative breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by local investigators

  PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.

  Up to 36 months

Secondary Outcomes (9)

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigators

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

• Objective Response Rate(ORR) in induction and maintenance phase

  Up to approximately 36 months

• Progression-Free Survival (PFS) in gBRCAm and gBRCAwt participants

  Up to approximately 36 months

• Overall Survival (OS) in gBRCAm and gBRCAwt participants

  Up to approximately 36 months

Other Outcomes (1)

• Molecular biomarkers that might be indicative of clinical response/resistance

  Up to approximately 36 months

Study Arms (2)

Cisplatin+ Nab-paclitaxel + Pembrolizumab followed by Pembrolizumab monotherapy

ACTIVE COMPARATOR

4\~6 cycles combination therapy of Cisplatin, Nab-paclitaxel and Pembrolizumab as induction therapy; Pembrolizumab monotherapy as maintenance therapy

Drug: Cisplatin; Drug: Nab-paclitaxel; Drug: Pembrolizumab

Cisplatin+Nab-paclitaxel+Pembrolizumab followed by Pembrolizumab+Olaparib

EXPERIMENTAL

4\~6 cycles combination therapy of Cisplatin, Nab-paclitaxel and Pembrolizumab as induction therapy; Pembrolizumab plus Olaparib as maintenance therapy

Drug: Cisplatin; Drug: Nab-paclitaxel; Drug: Pembrolizumab; Drug: Olaparib

Interventions

Cisplatin DRUG

75 mg/m2 IV days 1 of each 21-day cycle

Cisplatin+ Nab-paclitaxel + Pembrolizumab followed by Pembrolizumab monotherapy; Cisplatin+Nab-paclitaxel+Pembrolizumab followed by Pembrolizumab+Olaparib

Nab-paclitaxel DRUG

125 mg/m2 IV days 1 and 8 of each 21-day cycle

Cisplatin+ Nab-paclitaxel + Pembrolizumab followed by Pembrolizumab monotherapy; Cisplatin+Nab-paclitaxel+Pembrolizumab followed by Pembrolizumab+Olaparib

Pembrolizumab DRUG

200 mg IV every 21 days

Also known as: keytruda

Cisplatin+ Nab-paclitaxel + Pembrolizumab followed by Pembrolizumab monotherapy; Cisplatin+Nab-paclitaxel+Pembrolizumab followed by Pembrolizumab+Olaparib

Olaparib DRUG

300 mg PO BID

Also known as: LYNPARZA

Cisplatin+Nab-paclitaxel+Pembrolizumab followed by Pembrolizumab+Olaparib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Induction period:
• Locally advanced, recurrent or metastatic TNBC that has not been treated with chemotherapy for the advanced disease. Local or distant disease recurrence must be≥6 months from the completion of the last dose of chemotherapy.
• PD-L1 CPS≥1 and ER and PR negative, HER2 negative breast cancer.
• Archival tumor tissue sample or newly obtained core or excisional biopsy sample
• Measurable disease based on RECIST 1.1.
• ECOG Performance Status 0-1
• Life expectancy≥18 weeks
• Adequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 10 days prior to start of study treatment)
• Maintenance period：
• Complete induction therapy without permanent discontinuation of pembrolizumab, nab-paclitaxel or cisplatin.
• CR, PR, or SD status based on RECIST 1.1 as determined by local investigators.
• ECOG Performance Status 0-1, as assessed within 7 days prior to the start of maintenance therapy.
• Recovery of toxicities related to induction therapy to ≤ grade 1 (except alopecia) prior to randomization. Grade 2 neuropathy will be allowed, whereas grade 2 hyperthyroidism or hypothyroidism will also be allowed if it can be well controlled with medicines.

You may not qualify if:

• Induction period:
• Has received any prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received any prior therapy with either olaparib or other PARP inhibitors.
• Has received any prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study treatment
• Has received a live vaccine within 30 days prior to the first dose of study drug
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, cervical cancer in situ) that have undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has a known history of hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipient
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has gastrointestinal impairment that could affect their ability to take or absorb oral medicines; evidence of severe or uncontrolled cardiac disease; active bleeding or bleeding diathesis defined as significant hemorrhage; or hemoptysis.
• Has a resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions or has congenital long QT syndrome.
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML

Sponsors & Collaborators

• Fudan University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Cisplatin; 130-nm albumin-bound paclitaxel; pembrolizumab; olaparib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. , ph.D.

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: January 3, 2022
• Study Start: September 7, 2022
• Primary Completion: December 1, 2023
• Study Completion: March 1, 2025
• Last Updated: September 28, 2023

Record last verified: 2022-11

Locations

CN (1)