ZEN-3694 + Pembrolizumab + Chemotherapy for Breast Cancer
Recruiting in Palo Alto (17 mi)
+4 other locations
Overseen byAna C Garrido-Castro
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: CYP3A4 inhibitors, Factor Xa inhibitors
Disqualifiers: Autoimmune disease, GI disorder, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase Ib trial tests the safety and tolerability of ZEN003694 in combination with an immunotherapy drug called pembrolizumab and the usual chemotherapy approach with nab-paclitaxel for the treatment of patients with triple negative-negative breast cancer that has spread to other parts of the body (advanced). Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Immunotherapy with monoclonal antibodies, such as pembrolizumab may help the body's immune system attach the cancer and may interfere with the ability of tumor cells to grow and spread. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Combination therapy with ZEN003694 pembrolizumab immunotherapy and nab-paclitaxel chemotherapy may help shrink or stabilize cancer for longer than chemotherapy alone.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot take strong inhibitors or inducers of CYP3A4, Factor Xa inhibitors, or Factor IIa inhibitors. It's important to discuss your current medications with the study team to ensure there are no interactions.
Is the combination of ZEN-3694, Pembrolizumab, and nab-paclitaxel safe for humans?
Nab-paclitaxel, a component of the treatment, is generally considered safe and is approved for use in several cancers, including breast cancer, with known side effects. It was developed to avoid certain toxicities associated with older formulations. However, specific safety data for the combination with ZEN-3694 and Pembrolizumab is not provided in the available research.
12345What makes the drug combination of ZEN-3694, Pembrolizumab, and Nab-paclitaxel unique for breast cancer treatment?
This drug combination is unique because it combines ZEN-3694, a novel drug, with Pembrolizumab, an immune therapy, and Nab-paclitaxel, a chemotherapy that avoids certain toxicities, offering a potentially more effective and safer treatment option for breast cancer patients.
12567Eligibility Criteria
This trial is for adults with advanced triple-negative breast cancer that's spread and can't be removed by surgery. Participants must have acceptable organ function, no severe prior reactions to similar drugs, and not be on certain medications that affect the study drugs. They should not have had recent chemotherapy or immunotherapy, and women of childbearing age must use contraception.Inclusion Criteria
I am willing and able to have tumor biopsies before and during treatment.
My kidney function is within the normal range.
I had hepatitis C but have been successfully treated and cured.
+32 more
Exclusion Criteria
I have a digestive condition that affects how my body absorbs pills.
I have never taken the study drug or any experimental BET inhibitors.
I am currently taking blood thinners that target Factor Xa or IIa.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Patients receive ZEN003694 orally once daily on days 1-21, nab-paclitaxel intravenously on days 1, 8, and 15, and pembrolizumab intravenously every 21 days of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Up to 35 cycles (28 days each)
3 visits per cycle (in-person)
Dose Expansion
Patients receive ZEN003694 orally once daily on days 1-7 prior to combination therapy, then continue with ZEN003694, nab-paclitaxel, and pembrolizumab as in dose escalation. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Up to 35 cycles (28 days each)
3 visits per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs 30 days after the last dose and then every 6 months for up to 3 years or until death.
Up to 3 years
Every 6 months
Participant Groups
The trial tests ZEN003694 (a BET protein inhibitor) combined with pembrolizumab (an immunotherapy drug) and nab-paclitaxel (a form of chemotherapy). It aims to see if this combination is safer and more effective than standard treatments in shrinking or stabilizing cancer.
2Treatment groups
Experimental Treatment
Group I: Dose Expansion (ZEN003694, nab-paclitaxel, pembrolizumab)Experimental Treatment7 Interventions
Patients receive ZEN003694 PO QD on days 1-7 prior to combination therapy. Patients then receive ZEN003694 PO QD on days 1-21, nab-paclitaxel IV over 30 minutes on days 1, 8, and 15, and pembrolizumab IV over 30 minutes every 21 days of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity with a maximum of 35 doses of pembrolizumab administered. Patients also undergo biopsies on study, and CT or MRI scans and collection of blood samples throughout the trial.
Group II: Dose Escalation (ZEN003694, nab-paclitaxel, pembrolizumab)Experimental Treatment7 Interventions
Patients receive ZEN003694 PO QD on days 1-21, nab-paclitaxel IV over 30 minutes on day 1, 8, and 15, and pembrolizumab IV over 30 minutes every 21 days of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity with a maximum of 35 doses of pembrolizumab administered. Patients also undergo CT or MRI scan and collection of blood samples throughout the trial.
Nab-paclitaxel is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Abraxane for:
- Metastatic breast cancer
- Non-small cell lung cancer
- Adenocarcinoma of the pancreas
🇪🇺 Approved in European Union as Abraxane for:
- Metastatic breast cancer
- Non-small cell lung cancer
- Adenocarcinoma of the pancreas
🇨🇦 Approved in Canada as Abraxane for:
- Metastatic breast cancer
- Non-small cell lung cancer
- Adenocarcinoma of the pancreas
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
Vanderbilt Breast Center at One Hundred OaksNashville, TN
Dana-Farber - Harvard Cancer Center LAOBoston, MA
Boston Medical CenterBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Neoadjuvant Therapy with Weekly Nanoparticle Albumin-Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011-02), a Multicenter, Non-Randomized, Phase II Trial, with a Companion Biomarker Analysis. [2021]Nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab-Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) disease.
A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer. [2022]Nab-paclitaxel is a novel nanoparticle, albumin-bound, solvent-free, taxane-based chemotherapy approved for the treatment of metastatic breast cancer (MBC). This study reports clinical benefit and toxicities experienced by women with MBC treated with nab-paclitaxel.
A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]nab-Paclitaxel (ABI-007, Abraxane), a 130-nM, albumin-bound (nab) particle form of Cremophor-free paclitaxel, is approved for metastatic breast cancer. In the current study, the efficacy and safety of nab-paclitaxel were evaluated in previously treated and chemotherapy-naive patients with metastatic melanoma (MM).
Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]Nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane(®)) is FDA approved for the treatment of several adult cancers. Antimitotic agents are essential components for curative therapy of pediatric solid tumors, although taxanes have shown limited activity. Because of the novel formulation, nab-paclitaxel was evaluated against a limited series of Pediatric Preclinical Testing Program (PPTP) solid tumors.
Safety and efficacy evaluation of albumin-bound paclitaxel. [2015]Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free formulation of paclitaxel, which was developed to avoid toxicities associated with Cremophor EL® vehicle used in solvent-based paclitaxel. It is approved as monotherapy for treatment of metastatic breast cancer (MBC) in Europe and the US; in combination therapy for non-small-cell lung cancer (NSCLC) and for first-line treatment of advanced pancreatic cancer (PC) only in the US. The European Medicines Agency has recently released only a positive opinion for use of nab-paclitaxel in PC.
First-Line Pembrolizumab Plus Chemotherapy for Advanced Squamous NSCLC: Real-World Outcomes at U.S. Oncology Practices. [2023]Pembrolizumab plus carboplatin and (nab-)paclitaxel (pembrolizumab-chemotherapy) is currently an approved and recommended systemic therapy for patients with previously untreated advanced squamous NSCLC. This retrospective study evaluated real-world time on treatment (rwToT) and overall survival (OS) among patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy at oncology practices in the United States.
Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile. [2019]Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab-paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane.