Context Therapeutics Inc. (Nasdaq: CNTX), a women’s oncology company developing small molecule and immunotherapy treatments for breast and gynecological cancers, today announced that data from the window-of-opportunity clinical trial of onapristone extended release (ONA-XR) in postmenopausal patients with progesterone receptor positive (PR+) early breast cancer demonstrated ONA-XR significantly increased suppression of tumor cell proliferation. The data were presented today during the 2021 San Antonio Breast Cancer Symposium (SABCS).
The Phase 0 open-label, single-arm, multicenter ONAWA (SOLTI-1802) trial conducted by Spanish cancer research group SOLTI, enrolled 10 patients with ER+/PR+/HER2- negative tumors and levels of the cell proliferation marker "Ki67" above 10% to evaluate ONA-XR by the rate of Complete Cell Cycle Arrest (CCCR) determined by Ki-67 (≤2.7%) when administered for three weeks prior to surgery (Abstract #511). Secondary endpoints of the trial included safety and correlating biological activity with immunohistochemistry (IHC) of tumor expression (ER, PR, Ser294-PgR, CD24, CD44, ALDH1, Ki-67), estradiol, and progesterone blood levels, and gene expression profile (NanoString nCounter® Breast 360TM panel). While no patients achieved a CCCR, tumor Ki-67 expression decreased in six patients, remained stable in one patient, and increased in three patients. Mean percentage decrease of Ki67 for tumors with baseline PR expression ≥90% (N=4) and <90% (N=6) was -25.23% and 2.54%, respectively, indicating a trend towards enhance response for patients with high levels of PR expression at baseline. In addition, a shift towards more endocrine-sensitive disease was detected, implying an increased chance of the tumor responding to anti-estrogen therapy when used in combination with ONA-XR. Six patients reported adverse events (AEs), of which most were grade 1 or 2 including post-procedural pain, dry mouth, and an increase of gamma-glutamyl transferase (GGT). One patient experienced Grade 3 reversible GGT and aspartate aminotransferase (AST).
“The data from the ONAWA trial signal the potential of ONA-XR to help inhibit tumor proliferation and shift tumors to a more endocrine treatment-sensitive phenotype during treatment prior to surgery in postmenopausal women with operable breast cancer and improve overall prognosis for these patients,” said co-principal investigator Meritxell Bellet, M.D., Ph.D., medical oncologist at Vall d'Hebron University Hospital in Barcelona and an executive board member of SOLTI. “These results support further evaluation of ONA-XR in the treatment of early breast cancer.”
“ONA-XR is being evaluated in four investigator-sponsored clinical trials in hormone-driven breast, ovarian and endometrial cancers. This readout is the first for the novel PR antagonist, and the results are encouraging early evidence of the potential of ONA-XR to offer a new therapeutic option for hormone-dependent cancers,” said Martin Lehr, CEO of Context Therapeutics. “We look forward to data updates from three other ONA-XR trials in 2022.”
The design of two additional clinical trials evaluating ONA-XR in metastatic breast cancer (MBC) were also presented in trials-in-progress posters during SABCS: The SMILE Study, a Phase 2 trial evaluating ONA-XR in combination with fulvestrant for patients with ER+ and HER2- metastatic breast cancer after progression on endocrine therapy and CDK4/6 inhibitors that is being conducted in collaboration with the Wisconsin Oncology Network (Abstract #311); and Memorial Sloan Kettering Cancer Center’s Phase 1b trial designed to define the safety, tolerability and recommended Phase 2 dose of ONA-XR in combination with letrozole and palbociclib, in addition to investigating the circulating tumor DNA-guided response of this triplet therapy regimen in high-risk patients (Abstract #1538).