Abstract OT1-05-02: A phase II clinical trial of the combination of pembrolizumab and selective androgen receptor modulator GTx-024 in patients with advanced androgen receptor positive triple negative breast cancer

1069 Background: Androgen receptor (AR) targeting therapy has shown single agent activity in triple negative breast cancer (TNBC). GTx-024, a nonsteroidal selective androgen receptor modulator (SARM), demonstrated preclinical and clinical activity in AR+ breast cancer. The current study is designed to test the safety and efficacy of GTx-024 and pembrolizumab in patients with AR+ metastatic TNBC (mTNBC). Methods: This is an open-label phase 2 study for AR+ mTNBC. Eligible participants receive pembrolizumab 200mg IV every 3 weeks in combination with GTx-024 18mg po daily. Key eligibility criteria include patients with AR+ ( > 10%, 1+ by IHC); mTNBC; ECOG 0-1; measurable disease per RECIST 1.1. Patients are excluded if they had prior checkpoint inhibitors or AR targeted agents. The primary objective is to evaluate the tolerability of GTx-024 and pembrolizumab, and determine the response rate. Results: Seventeen patients were enrolled in the study. One patient was ineligible due to previously undiagnosed brain metastases. Ten of 16 patients had visceral metastasis (lung or liver), and 15% of patients had received ≥ 3 previous lines of therapy for mTNBC. Among 16 patients evaluable for response, 2 patients achieved a best response of partial response (PR), 2 patient had stable disease (SD, 18 and 19 weeks ), 11 patients had progressive disease (PD), and 1 patient is too early for restaging imaging. Durable response was found in 1 patient. Grade 3 toxicities include 1 diarrhea and 1 dry skin. Grade 2 adverse events include 3 elevated liver function, 1 adrenal insufficiency, 1 hyperthyroidism, 1 palpitation, 1 diarrhea, 1 hyperhydrosis, 1 hot flashes and 1 headache. Three patients had dose delay and two patients had dose reduction. Conclusions: AR targeted therapy GTx-024 combined with pembrolizumab is well tolerated with clinical activity. Clinical trial information: NCT02971761.

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A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic triple negative breast cancer

Cancer Biology & Therapy ◽

10.1080/15384047.2015.1026481 ◽

2015 ◽

Vol 16 (5) ◽

pp. 678-683 ◽

Cited By ~ 15

Author(s):

S Cowherd ◽

L D Miller ◽

S A Melin ◽

S Akman ◽

S Isom ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Phase Ii ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Phase Ii Clinical Trial ◽

Weekly Paclitaxel

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TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2014.57.6660 ◽

2015 ◽

Vol 33 (17) ◽

pp. 1902-1909 ◽

Cited By ~ 215

Author(s):

Steven J. Isakoff ◽

Erica L. Mayer ◽

Lei He ◽

Tiffany A. Traina ◽

Lisa A. Carey ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Clinical Trial ◽

Homologous Recombination ◽

Phase Ii ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Phase Ii Clinical Trial ◽

End Points ◽

Homologous Recombination Deficiency

Purpose The identification of patients with metastatic triple-negative breast cancer (mTNBC) who are expected to benefit from platinum-based chemotherapy is of interest. We conducted a single-arm phase II clinical trial of single-agent platinum for mTNBC with biomarker correlates. Patients and Methods Patients with mTNBC received first- or second-line cisplatin (75 mg/m2) or carboplatin (area under the concentration-time curve 6) by physician's choice once every 3 weeks. Coprimary end points were objective response rate (RR) and response prediction by p63/p73 gene expression. Secondary and exploratory end points included toxicity assessment, RR in cisplatin versus carboplatin, and RR in molecularly defined subgroups, including BRCA1/2 mutation carriers. Results Patients (N = 86; 69 as first-line therapy) received cisplatin (n = 43) or carboplatin (n = 43). RR was 25.6% (95% CI, 16.8% to 36%) and was numerically higher with cisplatin (32.6%) than with carboplatin (18.7%). RR was 54.5% in patients with germline BRCA1/2 mutations (n = 11). In patients without BRCA1/2 mutations (n = 66), exploratory analyses showed that a BRCA-like genomic instability signature (n = 32) discriminated responding and nonresponding tumors (mean homologous recombination deficiency–loss of heterozygosity/homologous recombination deficiency–large-scale state transitions [HRD-LOH/HRD-LST] scores were 12.68 and 5.11, respectively), whereas predefined analysis by p63/p73 expression status (n = 61), p53 and PIK3CA mutation status (n = 53), or PAM50 gene expression subtype (n = 55) did not. Five of the six long-term responders alive at a median of 4.5 years lacked germline BRCA1/2 mutations, and two of them had increased tumor HRD-LOH/HRD-LST scores. Conclusion Platinum agents are active in mTNBC, especially in patients with germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify patients without mutations who could benefit from platinum therapy agents. Prospective controlled confirmatory trials are warranted.

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