On December 13, 2019 OncoSec Medical Incorporated ("OncoSec") (Nasdaq:ONCS), a company developing late-stage intratumoral cancer immunotherapies, reported interim results from KEYNOTE-890, an ongoing Phase 2 study of TAVO (intratumoral IL-12) in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 checkpoint inhibitor, in patients with metastatic, chemotherapy-refractory triple negative breast cancer (mTNBC) (Press release, OncoSec Medical, DEC 13, 2019, View Source [SID1234552363]).
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Patients who previously had progressed after an average of three prior lines of chemotherapy were enrolled in the KEYNOTE-890 study to evaluate if the addition of TAVO could provide meaningful clinical activity when combined with KEYTRUDA. The interim analysis, presented on December 12, 2019, at the San Antonio Breast Cancer Symposium, included more than half of the patients (14 out of 25) enrolled in the KEYNOTE-890 study evaluating tumor responses, related immunological responses and safety.
Four of the 14 patients showed a rapid tumor reduction and had a confirmed partial response by RECIST v1.1 (ORR 28.5%), including a deep partial response in a patient with multiple liver, bone, skin and nodal metastases and a short disease-free interval following neoadjuvant chemotherapy. All responses are ongoing (range: 6 to 9 months) and a median duration of response (DOR) has not yet been reached. Three of the four patients with a partial response experienced deepening tumor shrinkage over six months.
These interim findings compare favorably to the response rate (range of 6-10%) observed with KEYTRUDA as a monotherapy in mTNBC patients 1,2.
Stable disease was observed in three patients (21.4%), with two stable disease patients reporting 20% or greater tumor shrinkage. Of the seven patients who progressed following treatment, two received only one cycle of combination treatment prior to rapid clinical deterioration. Regression of both TAVO treated and untreated lesions were observed. Regression of distal visceral lesions were also observed. Additionally, 3 of the 4 responding patients’ lesions were PD-L1 negative by IHC analysis before treatment (1 patient was undetermined).
"Metastatic TNBC is a heterogeneous disease with a poor prognosis where very few pre-treated patients achieve an objective response to PD-1/PD-L1 checkpoint inhibitor therapy," said Melinda L. Telli, MD, Stanford University School of Medicine. "These preliminary data suggest that TAVO may enhance sensitivity to pembrolizumab in mTNBC patients with a 28.5% ORR reported. I’m encouraged by the tumor responses observed in PD-L1 negative patients and the overall safety profile."
Importantly, TAVO and pembrolizumab were well tolerated, with only 3 of 16 patients experiencing grade 3 treatment-related adverse events with combination treatment.
Patients demonstrated encouraging immunological responses in tumor and blood consistent with an IL-12-associated mechanism of action, including significantly increased on-treatment proliferating T cell subsets in the periphery and increased gene expression signatures associated with productive immunological responses in the tumor. Biomarker analysis of patient tumor and blood samples are ongoing.
"These data show a strong signal for clinical benefit with TAVO enhancing sensitivity to pembrolizumab in treating metastatic TNBC patients who were previously unresponsive to multiple prior rounds of therapy," said Kellie Malloy, Chief Clinical Development Officer at OncoSec. "They also confirm the consistent safety profile of TAVO as a well-tolerated cancer immunotherapy. We look forward to continuing development and plan to expand this clinical program and the KEYNOTE-890 trial."
To date, the KEYNOTE-890 study has enrolled 24 of the planned 25 patients. OncoSec expects to report the full data results in 2020.
About Triple Negative Breast Cancer (TNBC)
TNBC is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat. Approximately 10-20% of patients with breast cancer are diagnosed with TNBC.
About KEYNOTE-890
KEYNOTE-890 is designed as a multicenter Phase 2 open-label trial focusing on patients with a histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC and at least 1 prior line of approved systemic chemotherapy or immunotherapy. 25 patients are expected to be enrolled. Each patient will undergo 3-week treatment cycles with pembrolizumab administered as a 30-minute IV infusion day 1 of every cycle (flat dose of 200 mg) and treated with TAVO on days 1, 5 and 8 every six weeks.