Puma Biotechnology Announces Presentation of Findings from a Phase I/II Study of Alisertib and Pembrolizumab for Rb-Deficient Head and Neck Squamous Cell Carcinomas at the 2023 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting

Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced the poster presentation of a Phase I/II trial of alisertib plus pembrolizumab for the treatment of patients with Rb-deficient head and neck squamous cell carcinoma (Clinicaltrials.gov identifier NCT04555837) at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts. The poster (number LB_C12), entitled “Alisertib and pembrolizumab in Rb-deficient head and neck squamous cell carcinomas (HNSCC),” was presented by Faye M. Johnson, M.D., Ph.D., Department of Thoracic/Head & Neck Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, in the Late-breaking Poster Session C on Saturday, October 14 at 12:30 pm ET. A copy of the poster is available on the Puma website.

Alisertib is an adenosine triphosphate–competitive, reversible inhibitor of Aurora Kinase A (AURKA) that results in disruption of mitosis. Human papillomavirus (HPV) is a common cause of HNSCC, and infection leads to Retinoblastoma protein (Rb1) degradation. A synthetic lethal relationship between AURKA and Rb1 has been implicated preclinically, and alisertib has been shown to induce immunogenic cell death in HPV+ cancer cells.

The investigator-sponsored clinical trial was conducted sequentially in two parts: A Phase I study to determine the recommended dose for alisertib in combination with pembroluzimab in patients with advanced solid tumors, and a Phase II study to evaluate efficacy of alisertib and pembroluzimab in patients with recurrent or metastatic, Rb-deficient HNSCC who had progressed on prior anti-PD1 therapy. Biomarkers of response were also evaluated.

The Phase I portion of the study enrolled ten patients with advanced solid tumors. There was no requirement for Rb deficiency in the Phase I portion of the trial. Alisertib was dosed twice daily for seven days every twenty-one days at either 30 mg, 40 mg, or 50 mg, and pembrolizumab was dosed at 200 mg intravenously every three weeks. The observed dose-limiting toxicities were predominantly hematologic in nature and congruent with the expected safety profile. Based on these findings, the 40 mg dose level was selected for the Phase II portion of the study. The Phase I portion of the trial enrolled patients with several different solid tumors including small cell lung cancer, thyroid carcinoma showing thymic-like differentiation, oropharynx cancer, salivary cancer and head and neck squamous cell carcinoma. One patient with small cell lung cancer experienced stable disease lasting for 245 days, one patient with HPV-positive orpharynx cancer experienced stable disease lasting for 209 days, and one patient with thyroid carcinoma showing thymic-like differentiation experienced stable disease lasting 811+ days.

Fourteen patients with immunotherapy- and platinum-resistant HPV+ HNSCC were enrolled in the Phase II portion of the study. Two of the fourteen patients had confirmed Rb1 loss by next generation sequencing. No objective responses were observed, though seven patients, including three with progression-free survival (PFS) exceeding 8 months, experienced stable disease. The remaining seven experienced progressive disease. The median PFS was 1.4 months, and the median overall survival (OS) was 13.5 months. No new safety signals were observed.

The relationships between biomarkers and response were evaluated. Baseline plasma cytokines IL-2, IL-10, IL-17 and IL-1b were lower in patients with PFS > 6 months than in those with PFS ≤ 6 months (p=0.0186, 0.0189, 0.0199, and 0.0098, respectively). Baseline PDL1 expression (Combined Positive Score (CPS)) did not demonstrate a correlation with PFS (p=0.59) or OS (p=0.96). An increase in circulating CD8+, CD4+ and CD56+ immune cells between baseline and Cycle 3 Day 1, assessed by polychromatic flow cytometry, was observed in patients with PFS > 6 months, but not in those with PFS ≤ 6 months. Finally, an increase in quantitative levels of HPV cell-free DNA compared to baseline corresponded with disease progression.

“There remains a need for better treatment options for HNSCC, particularly in the context of immune checkpoint therapy resistance,” said Dr. Johnson. “Although overall clinical response was modest, the combination of alisertib and pembrolizumab was well tolerated and led to prolonged stable disease in patients who had previously progressed on immunotherapy, supporting our hypothesis that Aurora Kinase A inhibition may reverse immunotherapy resistance in Rb-deficient HNSCC. These findings warrant further investigation into mechanisms to increase immunogenic cell death and apoptosis in Rb-deficient cancers treated with alisertib.”

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, “We are intrigued by the results of this trial and remain committed to and focused on the development of alisertib. The prospect of biomarker-defined populations who may benefit most from alisertib treatment continues to be an area of great interest.”

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX is a registered trademark of Puma Biotechnology, Inc.

In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer.

Further information about Puma Biotechnology may be found at https://www.pumabiotechnology.com.

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