Intensity Therapeutics, based in Westport, Conn., presented promising data on its intratumoral therapy INT230-6 at the SABCS. In a Phase I/II trial, the therapy is being tested with and without Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in heavily pre-treated refractory breast cancer patients.
INT230-6, which is injected directly into tumors, was discovered using the company’s proprietary DfuseRx technology platform. INT230-6 comprises two proven anti-cancer drugs, cisplatin and vinblastine, and an amphiphilic penetration enhancer molecule that helps spread the drugs through tumors—in addition to local disease control, killing cancer with the drug releases neoantigen specific to the patient’s cancer, which causes the immune system to activate further against cancer.
Seven patients were enrolled in the trial after seeing disease progression after a median of six (two to 10) previous therapies. The patients receiving INT230-6 by itself were more heavily pre-treated, with a median of eight previous therapies, compared to three in the Keytruda combination cohort. There was a 57% disease control rate (DCR), which was defined as the percentage of breast cancer patients with a complete response (CR), partial response (PR) or stable disease at the first radiologic assessment. There was a median overall survival (mOS) of 12 months, which is favorable compared to data seen in Phase I trials of people with highly refractory or triple-negative breast cancer.
Testing showed that 95% of vinblastine remained in the tumor. There was also a favorable safety pattern, with no serious treatment-related adverse events (TRAEs) in both cohorts. Only one participant had a grade 3 TRAE, and that was in the monotherapy group. There were no grade 4 or 5 TRAEs.
“Preliminary data suggests that INT230-6 demonstrates direct tumor killing in metastatic breast cancer subjects including those with triple-negative breast cancer (TNBC) and may elicit an anti-cancer immune response within the injected tumor with or without pembrolizumab,” said Philippe Bedard, M.D., clinician investigator, Princess Margaret Cancer Centre in Toronto, Canada, and the poster presenter. “Additionally, INT230-6 treatment-related adverse events are mostly low grade and the drug is well-tolerated either as a monotherapy or in combination with anti-PD-1 therapy, pembrolizumab. These results provide evidence to continue studying this novel therapeutic drug approach in breast cancer.”
In addition to this study, INT230-6 is being evaluated in other studies with various advanced solid tumors as part of Study IT-01, including in patients with advanced pancreatic, colon, squamous cell, and bile duct malignancies. The company is also testing INT230-6 with Bristol Myers Squibb’s anti-CTLA-4 antibody, Yervoy (ipilimumab), in advanced liver, breast, and sarcoma cancers.
Lewis H. Bender, president and chief executive officer of Intensity, stated, “The data presented at the San Antonio Breast Cancer Symposium using INT230-6 alone or in combination with pembrolizumab were generated from refractory breast cancer patients treated in the dose-escalation portion of our Phase I clinical study, IT-01, and these results are encouraging. We have also learned a great deal about our drug in breast cancer from our trial in metastatic patients and our Phase II randomized INVINCIBLE study, which is testing INT230-6 in breast cancer patients in a presurgical setting.”
Cambridge, Mass.-based Infinity Pharmaceuticals presented updated data from the ongoing MARIO-3 Phase II trial of eganelisib in combination with Roche’s Tecentriq (atezolizumab) and Abraxane (nab-paclitaxel) in frontline metastatic triple-negative breast cancer (TNBC). Eganelisib is an oral first-in-class immuno-oncology macrophage reprogramming therapeutic.
“Tumor reductions in 88.6% of evaluable patients were associated with a disease control rate of 81.4% in patients with PD-L1 negative tumors who are among the most challenging to treat,” said Hatem Soliman, M.D., MARIO-3 investigator and medical director, Clinical Trials Office at the Moffitt Cancer Center.
At the conference, Novartis announced new data on its Phase II BYLieve trial of Piqray (alpelisib). It is an ongoing Phase II, open-label, 3-cohort non-comparative trial of Piqray with endocrine therapy, including men and pre- and postmenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), advanced or metastatic breast cancer who have progressed on or after previous therapies, including CDK4/6 inhibitor plus endocrine therapy.
“Beyond illustrating the efficacy and safety of alpelisib, regardless of the duration of prior CDK4/6i treatment, the data provide meaningful insights into how alpelisib may benefit different subgroups of patients,” said Hope S. Rugo, M.D., director, Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.
Arvinas, based in New Haven, Conn., and New York’s Pfizer, announced an update on its Phase I trial of ARV-471 in locally advanced or metastatic ER-positive/HER2-negative breast cancer. ARV-471 is a novel PROTAC estrogen receptor degrader being co-developed by the companies. The drug demonstrated antitumor activity in CDK4/6 inhibitor-pretreated patients with a clinical benefit rate (CBR) of 40% in the 47 patients who could be evaluated. Three patients had confirmed partial responses (PR). The drug demonstrated a favorable tolerability profile.
“These results continue to suggest that ARV-471 has the potential to become a first-in-category treatment, and a new standard of care, for ER+/HER2- breast cancer patients,” said John Houston, Ph.D., chief executive officer at Arvinas.