On June 3, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing therapies designed to activate a patient’s immune system against cancer, reported compelling new interim results from its ongoing Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo) (Press release, Heat Biologics, JUN 3, 2019, View Source [SID1234536792]). The updated results were obtained from Cohort B patients whose data has matured an additional 3 months since last reported at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in February of this year. This data may represent the first Phase 2 data showing clinical activity in non-small cell lung cancer (NSCLC) patients whose disease has progressed after prior treatment with a checkpoint inhibitor (CPI). The Cohort B results were presented yesterday at the2019American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting poster session.
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COL(ret) George E Peoples, MD, FACS, Heat’s Chief Medical Advisor, noted, "These latest Cohort B data provides us even greater confidence that the addition of HS-110 to nivolumab may restore anti-tumor activity in patients whose disease has progressed after treatment with a CPI. Of particular note, 4 out of 5 evaluable patients in Cohort B with PD-L1 negative tumors achieved disease stabilization and 4 out of 7 evaluable patients with low CD8+ TIL levels in their tumors achieved disease stabilization. We are encouraged by these positive results and look forward to reporting additional data later this year."
Jeff Hutchins, Ph.D., Heat’s Chief Scientific and Operating Officer said, "The fact that we saw tumor shrinkage in 35% of patients and disease control in 55% of patients whose disease has progressed after treatment with a CPI supports our mechanistic hypothesis that the broad, T-cell mediated immune response activated by HS-110 may improve clinical outcomes for patients who have lost the benefit of treatment with a checkpoint inhibitor. It is also important to note that the occurrence of dermal injection site reactions is associated with statistically significant improved progression free survival and overall survival, providing further support for the mechanism of action of HS-110."
Highlights for Cohort B patients arepresented below:
HS-110 in combination with nivolumab demonstrates clinical activity i’difficult to treat’ low CD8+ TIL (≤10%) and PD-L1 negative (<1%) tumors:
4 out of 5 evaluable patients with PD-L1 negative tumors achieved disease stabilization, 1 of which was a RECIST partial response.
4 out of 7 evaluable patients with low CD8+ TIL tumors achieved disease stabilization, 2 of which were RECIST partial responses.
The addition of HS-110 to nivolumab may restore clinical benefit to patients whose disease has progressed after CPI treatment failure:
Tumor shrinkage observed in 35% of patients
Disease control rate of 55%
Median Progression-Free Survival (mPFS) of 2.7 months
Median Overall Survival (mOS) not yet reached
The occurrence of any grade dermal Injection Site Reaction during treatment (Y/N) is associated with improved Progression-Free Survival and Overall Survival:
mPFS: NR vs 1.8 months; HR 0.17 (95% CI, 0.03-0.84); p=0.013
mOS: NR vs 5 months; HR 0.13 (95% CI, 0.02-0.71); p=0.002
Treatment with HS-110 in combination with nivolumab was well tolerated, with no additional toxicities beyond those observed with single agent CPI therapy.
Trial results are summarized in the official 2019 ASCO (Free ASCO Whitepaper)Annual Meeting poster.
Trial Design
The Phase 2 trial is designed to evaluate the safety and efficacy of HS-110 combined with an immune checkpoint inhibitor for the treatment of advanced non-small cell lung cancer. Cohort B consists of patients who received a minimum of 4 months of treatment with a checkpoint inhibitor (CPI) as part of their prior therapy, but subsequently had documented progressive disease. Patients receive weekly HS-110 (1 x 107 cells) administered as 5 intradermal 0.1 mL injections for 18 weeks in combination with bi-weekly nivolumab 240 mg IV administered until confirmed disease progression or unacceptable toxicity, whichever occurs first. The primary endpoint is objective response rate (ORR); secondary endpoints include overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DOR). Exploratory endpoints include correlation of clinical outcomes to baseline CD8+ TILs, PD-L1 expression, peripheral blood tumor mutation burden and ELISPOT analysis.