Item 8.01 Other Events.
On November 12, 2021, the Company delivered a poster presentation at SITC's 36th Annual Meeting. The poster was titled "Initial results of a Phase 1 study of intratumoral ONCR-177, an oncolytic herpes-simplex virus-1 expressing five immunomodulatory transgenes, in subjects with advanced injectable tumors," presented by Jong Park, M.D., Instructor, Medicine, Harvard Medical School and Assistant, Medicine, Massachusetts General Hospital.
The data presented at SITC include preliminary findings from Part 1 of the Phase 1 clinical trial of ONCR-177, including data from 14 patients in the fully enrolled and completed dose escalation cohorts and five patients enrolled in the dose expansion monotherapy, as of November 1, 2021, the cut-off date for the SITC poster submission, in addition to incremental patient data as of November 8, 2021 that was presented live at SITC's 36th Annual Meeting. The key highlights from the presentation include:
In the fully enrolled and completed surface lesion dose escalation portion of the Phase 1 clinical trial, ONCR-177 administered to heavily pretreated patients with advanced, injectable solid tumors was well tolerated with no dose-limiting toxicities. In addition, the recommended Phase 2 dose (“RP2D”) was determined to be 4x108 PFU in 4 mL. No treatment-related adverse events exceeded Grade 3, and the most common Grade 1 and 2 adverse events were fatigue, chills, nausea, and mild, dose-dependent cytokine release syndrome (“CRS”). No infectious virions were detected in skin swabs, consistent with the Company's expectations with respect to ONCR-177's safety profile.
As of November 1, 2021, seven heavily pretreated patients had been enrolled in the ongoing surface lesion, histology-specific monotherapy expansion cohorts of the trial. As of such date, four of these patients were evaluable, one patient went off study after a single dose and is not evaluable, and two are too early in their treatment course to be evaluable.
The four evaluable monotherapy expansion patients referred to above are in addition to four evaluable monotherapy escalation patients treated at the RP2D. As of November 8, 2021, after four weeks of monotherapy treatment with ONCR-177 at RP2D (two doses), three of eight evaluable patients (one with cutaneous melanoma, one with squamous cell carcinoma of the head and neck (“SCCHN”), and one with mucosal melanoma) demonstrated clinical benefit as follows:
Partial response in a patient with cutaneous melanoma as measured by calipers per Response Evaluation Criteria in Solid Tumors (“RECIST”) 1.1 (the surface tumor was not measurable by CT scan);
Investigator-reported clinical response in a SCCHN patient in injected lymph node after four weeks; and
Stable disease in a patient with mucosal melanoma as measured by RECIST 1.1 with improvement in cancer-related symptoms.
Several findings from the study thus far suggest immune stimulation of the tumor microenvironment, including mild, dose-dependent CRS in association with increased interferon-g (IFN-g) and T-cell proliferation in blood, as well evidence of tumor PD-L1 expression and immune cell infiltration.
The Company plans to initiate patient enrollment in the surface lesion dose combination expansion (Part 2 of the clinical trial) and the visceral lesion dose monotherapy escalation (Part 3 of the clinical trial) by the end of 2021. The Company also plans to report additional surface lesion monotherapy expansion data in mid-2022, and initial surface lesion combination expansion data (ONCR-177 administered in combination with Merck's KEYTRUDA® (pembrolizumab)) and visceral lesion monotherapy dose escalation data in late 2022.
Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the clinical development of ONCR-177, including expectations regarding timing for reporting additional data from the ongoing Phase 1 clinical trial, as well as the product candidate’s therapeutic potential and clinical benefits and the utility and potential of the Company's HSV Platform; the possibility that additional patients will experience clinical benefits when dosed with ONCR-177 and whether such treatment effects will be amplified when ONCR-177 is dosed in combination with Keytruda; and other early findings with respect to the ONCR-177 clinical trial suggesting broader immune stimulation or being predictive of trial results to come. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,”
"project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this Current Report on Form 8-K are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this Current Report on Form 8-K, including, without limitation, risks associated with: the risk that the results of preclinical studies and early results from clinical trials may not be predictive of future clinical trial results; the impact of COVID-19 on the Company's operations and the timing and anticipated results of its ongoing and planned clinical trials; the Company's ability to successfully demonstrate the safety, tolerability and efficacy of ONCR-177, or any future product candidates, and obtain regulatory approval thereof; the Company's ability to obtain the requisite components for its product candidates manufactured in accordance with regulatory requirements; the expansion of the Company's in-house manufacturing capabilities; the adequacy of the Company's cash resources and availability of financing on commercially reasonable terms; and the Company's ability to obtain, maintain and protect its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission on March 10, 2021, as well as discussions of potential risks, uncertainties, and other important factors in the other filings that the Company makes with the Securities and Exchange Commission from time to time. Any forward-looking statements represent the Company's views only as of the date of this Current Report on Form 8-K and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.