Combination Chemotherapy + Immunotherapy for Breast Cancer
(ToPCourT Trial)
Recruiting in Palo Alto (17 mi)
Overseen byAntoinette Tan, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Wake Forest University Health Sciences
Must not be taking: Corticosteroids, Immunosuppressive drugs
Disqualifiers: CNS metastases, Active infection, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The goal of this phase II study is to test the combination of trilaciclib, pembrolizumab, gemcitabine, and carboplatin in locally advanced unresectable or metastatic triple-negative breast cancer.
The main questions it aims to answer are:
* to evaluate the anti-cancer efficacy (assess how well it works)
* to evaluate the safety and tolerability (how well the body can handle the treatment) of this combination of anti-cancer therapy
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement to not have had prior systemic anti-cancer therapy within 3 weeks before starting the study treatment.
What data supports the effectiveness of the drug combination chemotherapy and immunotherapy for breast cancer?
Research shows that the combination of gemcitabine and carboplatin is active in treating metastatic breast cancer, with response rates up to 80% in untreated patients. Additionally, pembrolizumab combined with chemotherapy has shown improved outcomes in other cancers, like lung cancer, suggesting potential benefits in breast cancer as well.
12345Is the combination of chemotherapy and immunotherapy generally safe for humans?
Pembrolizumab, an immunotherapy drug, has been used safely in combination with chemotherapy for treating advanced lung cancer, but it can cause side effects like pneumonitis (lung inflammation) in 1%-5% of patients. This suggests that while generally safe, there are potential risks that need monitoring.
36789What makes this breast cancer treatment unique?
This treatment combines chemotherapy drugs (Carboplatin and Gemcitabine) with an immunotherapy drug (Pembrolizumab) and a supportive drug (Trilaciclib) that may protect bone marrow during chemotherapy, making it a novel approach by integrating both cancer-fighting and protective strategies.
1351011Eligibility Criteria
This trial is for adults with advanced triple-negative breast cancer that hasn't spread to the brain. Participants must have negative hormone receptor tests, be expected to live at least 12 weeks, and have measurable disease. They should understand the study procedures and agree to provide tissue samples. Women of childbearing age must test negative for pregnancy and use contraception.Inclusion Criteria
Subject agrees to use contraception
I am 18 years old or older.
You have a disease that can be measured using specific guidelines for evaluating solid tumors.
+9 more
Exclusion Criteria
I am allergic to carboplatin, gemcitabine, mannitol, or pembrolizumab.
You have active hepatitis B.
Pregnant or breastfeeding
+17 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive trilaciclib, pembrolizumab, gemcitabine, and carboplatin until disease progression, unacceptable toxicity, or withdrawal
Up to 2 years
Every 21 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The trial is testing a combination of drugs: Trilaciclib, Pembrolizumab (an immunotherapy), Gemcitabine, and Carboplatin in patients with metastatic triple-negative breast cancer. It aims to assess how effective this mix is against cancer and how well patients tolerate it.
1Treatment groups
Experimental Treatment
Group I: Trilaciclib, Pembrolizumab, Gemcitabine, and CarboplatinExperimental Treatment4 Interventions
Trilaciclib is an agent that helps protect the bone marrow from the side effects of chemotherapy. It is given as an intravenous (IV) infusion over 30 minutes prior to gemcitabine and carboplatin. Gemcitabine is given IV over 30 minutes. Carboplatin is given over 30 minutes. Trilaciclib, gemcitabine and carboplatin are given on Days 1 and 8 every 21 days. Pembrolizumab is given IV over 30 minutes on Day 1 every 21 days.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Levine Cancer InstituteCharlotte, NC
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Who Is Running the Clinical Trial?
Wake Forest University Health SciencesLead Sponsor
G1 Therapeutics, Inc.Industry Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Phase II trial of gemcitabine/carboplatin (plus trastuzumab in HER2-positive disease) in patients with metastatic breast cancer. [2022]Gemcitabine and carboplatin have significant preclinical synergy, and both provide synergistic antitumor activity in metastatic breast cancer (MBC) when used in combination with trastuzumab. The gemcitabine/ cisplatin combination is highly active in MBC with response rates (RRs) of approximately 50% in anthracycline- and taxane-pretreated patients and up to 80% in untreated subjects. This phase II trial studied the efficacy and safety of gemcitabine/carboplatin with or without trastuzumab in patients with MBC.
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.
Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.
Carboplatin and gemcitabine combination in metastatic triple-negative anthracycline- and taxane-pretreated breast cancer patients: a phase II study. [2022]Triple-negative breast cancer (TNBC) is characterized by lack of hormone receptors and HER-2 and shares many features with BRCA1-associated cancer. Preclinical data indicate cisplatin sensitivity, suggesting that these tumors may have defects in the BRCA1 pathway. The carboplatin and gemcitabine (CG) combination is active in unselected anthracycline/taxane pretreated metastatic breast cancer patients, so we carried out a phase II study to evaluate the activity of the CG combination in pretreated metastatic TNBC patients. From 10/2004 to 3/2009 we enrolled 31 patients. Median age was 57 years and 29 patients out of 31 had visceral involvement. The overall response rate (ORR) was 32% (1 complete response /9 partial responses), in addition 5 patients obtained stable disease for >12 weeks. After a median follow-up of 34 months, all patients progressed with a median time to progression of 5.5 months and median overall survival of 11 months. Dose reductions, delays and omissions occurred in 75 (60%), 36 (29%) and 22 (18%) cycles. Grade 3/4 neutropenia occurred in 17 and febrile neutropenia in 4 patients. Ten patients had Grade 3/4 thrombocytopenia. Non hematological toxicities were manageable. The CG combination is a reasonable option for the treatment of metastatic pretreated TNBC patients.
Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). [2023]BRCA1/2-related metastatic breast cancers (mBC) are sensitive to DNA-damage agents and show high tumor-infiltrated lymphocytes. We hypothesized that the association between pembrolizumab and carboplatin could be active in BRCA-related mBC.
Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. [2022]Anti-programmed death 1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies have shown modest activity as monotherapy in recurrent ovarian cancer. Platinum chemotherapies induce T-cell proliferation and enhance tumor recognition. We assessed activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer.