Intratumoral CD8+ T cells boosted following vaccination

DURHAM, N.C.—Heat Biologics, Inc., an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, announced results from its Phase 1 trial to evaluate safety and immune response to HS-410 (vesigenurtacel-L), after standard of care Bacillus Calmette-Guérin (BCG), for the treatment of high-risk, non-muscle invasive bladder cancer (NMIBC). HS-410 had a positive safety profile and was well-tolerated with no patients discontinuing the trial due to adverse events. Furthermore, no serious adverse events were reported, and 7 out of 10 patients had no documented recurrence of cancer >1 year after standard of care surgery. Significantly, 3 out of 4 patients with carcinoma in situ (CIS), the patient population least responsive to standard of care, did not recur.

HS-410 elicited a broad-based (polyclonal) expansion of patient T cells and a high level of CD8+  tumor-infiltrating lymphocytes (TILs), which are essential to an effective anti-tumor response. Additionally, HS-410 shared 15 or more tumor antigens in common with those expressed on the patients’ cancer cells, indicating HS-410’s ability to target a broad range of tumor antigens for all patients treated to date. These data confirm previous clinical findings regarding the unique mechanism of action for HS-410 and for the company’s ImPACT and ComPACT platform technologies.

Moreover, third-party analysis of blinded samples established a strong correlation between baseline characteristics of TILs by T cell receptor (TCR) sequencing and clinical outcome. Specifically, the 7 patients who remain disease free exhibited the greatest clonal expansion of intratumoral T cells (p-value 0.0126).

“We are delighted to see an immune response within tumors that is consistent with the HS-410 mechanism of action and which correlates with clinical outcome. Specifically, we see that HS-410 has a high degree of overlap with patient tumor antigens, stimulates polyclonal T cell proliferation and leads to a distinct immune signature in responding to patient tumors,” said Taylor Schreiber, M.D., Ph.D., Heat’s chief scientific officer. “Analysis of the pre- and post-treatment biopsies provides clear evidence that the HS-410-stimulated immune response reaches the tumor microenvironment and increases CD8+ T cells at levels which have not been published for other vaccines or BCG alone.”

“Conversion of tumors from low TIL density to high TIL density following treatment with HS-410 holds great promise for the treatment of the majority of cancer patients who have tumors that are initially TIL negative and have limited response to cancer immunotherapy,” added Llew Keltner, M.D., Ph.D., associate professor, Case Western Reserve University School of Medicine.

“HS-410 has been demonstrated to be well-tolerated by these patients, with no patients discontinuing treatment due to adverse events. This trend is in contrast to intravesical agents like BCG where the discontinuation rate is significant (approximately 25 percent),” said Gary D. Steinberg, M.D., professor of surgery and director, urologic oncology, at The University of Chicago Medicine, and lead study investigator. “Additionally, HS-410 is easy to administer and the level of patient interest is high for this intradermal therapy. As we prepare for Phase 3, we look forward to the Phase 2 results to extend this dataset with the combination therapy, as well as HS-410’s potential as a monotherapy without BCG.”

For its ongoing Phase 2 trial, Heat recently announced that it has completed enrollment of the full 75 patients in the three blinded, randomized, placebo-controlled arms evaluating HS-410 in combination with BCG. Heat remains focused on enrolling the additional 25 patients for the one unblinded, open-label monotherapy arm. Topline efficacy, immune-response and safety data are expected in the fourth quarter of 2016.

The Phase 1 data were summarized in a poster entitled “Phase 1 Study of Patients with Non-Muscle Invasive Bladder Cancer (NMIBC) Treated with Vesigenurtacel-L (HS-410) After Bacillus Calmette-Guérin (BCG)” presented at the Society for Immunotherapy of Cancer (SITC) 30^th Anniversary Annual Meeting & Associated Programs. The poster is accessible on Heat’s corporate website at https://www.heatbio.com/news/events-presentations.

HS-410 is an investigational product candidate for NMIBC based on Heat’s proprietary ImPACT immunotherapy platform, designed to generate CD8+ “killer” T cells that attack cancer cells. HS-410 is currently being evaluated in an ongoing Phase 2, placebo-controlled, 100-patient NMIBC trial at multiple centers and has been granted U.S. FDA Fast Track Designation for the treatment of NMIBC. Topline data from the Phase 2 trial are anticipated in the fourth quarter of 2016.

According to the American Cancer Society, bladder cancer is the fifth most common cancer in the U.S., with approximately 75,000 new cases and 16,000 deaths in 2015. About 75 percent of the newly diagnosed patients have NMIBC. A key issue for bladder cancer is the high rate of recurrence, for which limited treatment options are available beyond complete bladder removal.

The Phase 1 open-label, multicenter safety trial tested HS-410, after standard of care BCG, in 10 patients with NMIBC. Patients received the standard BCG treatment for 3-6 weeks, followed by weekly intradermal injections of HS-410 for 12 weeks and subsequent monthly HS-410 injections for 3 months. Subsequent maintenance BCG was administered at the discretion of the study investigator.

Heat Biologics, Inc. is an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer. Heat’s highly specific T cell-stimulating platform technologies, ImPACT and ComPACT, form the basis of its product candidates. These platforms, in combination with other therapies, such as checkpoint inhibitors, are designed to address three distinct but synergistic mechanisms of action: robust activation of CD8+ “killer” T cells (one of the human immune system’s most potent weapons against cancer); reversal of tumor-induced immune suppression; and T cell co-stimulation to further enhance patients’ immune response. Currently, Heat is conducting a Phase 2 trial with its HS-410 (vesigenurtacel-L) in patients with non-muscle invasive bladder cancer (NMIBC) and a Phase 1b trial with its HS-110 (viagenpumatucel-L) in combination with an anti-PD-1 checkpoint inhibitor to treat patients with non-small cell lung cancer.