On November 18, 2022 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported that clinical and translational data from the final analyses of the pivotal SPEARHEAD-1 trial (Cohort 1) with afamitresgene autoleucel (afami-cel) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) at the Connective Tissue Oncology Society (CTOS) annual meeting taking place this week in Vancouver, BC (Press release, Adaptimmune, NOV 18, 2022, View Source [SID1234624248]). The data will be shared in an oral presentation by SPEARHEAD-1 investigator, Brian A. Van Tine, MD, PhD, Washington University School of Medicine in St. Louis, on Friday, November 18th, during Session 9: Immunology & Immunotherapy at 4:39 p.m. UTC/ 7:30 p.m. EST (Paper 61).​

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"With these results, we continue our excitement and optimism about the clear potential of afami-cel to address synovial sarcoma- a difficult-to-treat cancer with high unmet need," said Elliot Norry, Chief Medical Officer, Adaptimmune. "These data reaffirm our commitment to this therapy, and we are very pleased to be able to include these data in our upcoming BLA submission."

Data reinforce clinical efficacy and acceptable safety profile of Adaptimmune’s novel T-cell therapy, afami-cel (August 29, 2022 data cut)

Data continue to support BLA submission for afami-cel in heavily pre-treated patients with synovial sarcoma with an overall response rate of 38.6% by independent review (N=44)
Responses are durable with a median duration of 50 weeks (range: 11.7-122 weeks)
Toxicities include cytokine release syndrome and reversible hematologic toxicities, in line with previous findings indicating an acceptable safety profile
Responses were observed across all evaluated subpopulations​ with higher response rates observed in female patients and those who had higher MAGE-A4 expression, had lower disease burden at baseline, or did not require bridging therapy. Data are consistent with those presented earlier this year as ASCO (Free ASCO Whitepaper)
Translational data indicate that afami-cel drives tumor infiltration of activated and proliferative cytotoxic ("killer") T-cells, shifting the balance from immune-suppressive to a pro-immune in the tumor microenvironment which likely contributes to antitumor response
"We are on the cusp of an exciting and important time for people impacted by synovial sarcoma, a cancer that for much too long has not seen innovative treatment options," said Dr. Brian A. Van Tine, Professor of Medicine and Pediatrics at Washington University School of Medicine in St. Louis. "The SPEARHEAD-1 Trial results provide us a reason to be very optimistic about the game-changing potential to treat more people with this difficult cancer in the very near future."

As previously announced, Cohort 1 of the SPEARHEAD-1 trial has completed treatment and met the primary endpoint for efficacy. Data from Cohort 1 will be used to support Adaptimmune’s BLA submission. Cohort 2 of the SPEARHEAD-1 trial is ongoing with treatment 60% complete and an overall response rate nearly identical to Cohort 1. On September 28th, Adaptimmune received the Vision of Hope Award from the Sarcoma Foundation of America at its Annual Stand Up to Sarcoma Gala.

SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a Phase 1 trial (CTOS 2020). Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only and will be used to support a BLA filing, which is expected to be initiated in Q4 2022.

No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses. Key eligibility criteria: ECOG performance status of 0 or 1; HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 16 and ≤ 75 years; and patients must have received either an anthracycline- or ifosfamide-containing regimen. Eligible patients received afami-cel doses between 1-10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.

On November 18, 2022 Kintara Therapeutics, Inc.(Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported data from three posters that are being presented at the 2022 Society for Neuro-Oncology (SNO) Annual Meeting (Press release, Kintara Therapeutics, NOV 18, 2022, View Source [SID1234624247]). The 2022 SNO Annual Meeting is being held from November 16 through November 20, 2022 in Tampa, Florida.

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Three posters on VAL-083 are being presented as follows:

Phase 2 Study of VAL-083 and Radiotherapy in Newly-Diagnosed, MGMT-unmethylated GBM
Poster Presenter: Zhongping Chen, MD, Ph.D. – Sun Yat-sen University Cancer Center
(Presentation Time: Friday, November 18, 2022 – 7:30 to 9:30 pm ET)

The first poster presented two case reports from the open-label, Phase 2 study of VAL-083 as a first-line treatment in newly-diagnosed, unmethylated GBM patients conducted at Sun Yat-sen University Cancer Center in China. These two patients, a 32-year-old woman and a 49-year-old man, have remained alive 53 months and 35 months, respectively, as of the October 2022 poster cut-off date.

Recurrent RELA Fusion-Positive Ependymoma Treated with VAL-083 under Expanded Access: A Case Report
Poster Presenter: Carlos Kamiya-Matsuoka, MD – MD Anderson Cancer Center
(Presentation Time: Friday, November 18, 2022 – 7:30 to 9:30 pm ET)

The second poster reported on a patient with recurrent RELA fusion-positive ependymoma who was treated with VAL-083 for 12 cycles under expanded access. Eighteen months after completion of treatment with VAL-083, the patient remains neurologically and radiologically stable with no evidence of disease.

VAL-083 in Patients with Recurrent Glioblastoma Treated under Expanded Access Program
Poster Presenter: Carlos Kamiya-Matsuoka, MD – MD Anderson Cancer Center
(Presentation Time: Friday, November 18, 2022 – 7:30 to 9:30 pm ET)

The third poster presented information on fourteen patients with recurrent GBM who were treated at MD Anderson Cancer Center under expanded access. Eight of these patients received four or more cycles of VAL-083, with one patient receiving 18 cycles. Data was also presented for five patients who received VAL-083 in combination with bevacizumab without any hematological adverse events.

On November 18, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused on driving innovation to transform outcomes for cancer patients, reported the presentation of preclinical data for ONCR-719 in a poster at the 2022 Society for Neuro-Oncology (SNO) Annual Meeting, taking place November 17-20, 2022 in Tampa, Florida (Press release, Oncorus, NOV 18, 2022, View Source [SID1234624242]).

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ONCR-719 is a novel, armed oncolytic HSV-1 vector engineered with targeted entry via EGFR/EGFRvIII and expresses four immunomodulatory payloads designed to reverse GBM’s immunosuppressive tumor microenvironment. In addition, ONCR-719 is derived from a potent HSV-1 isolate to drive oncolysis, is engineered with fusogenic mutations to enhance viral spread, and uses Oncorus’ clinically validated microRNA attenuation strategy to inhibit viral replication in healthy cells.

Highlights from the preclinical poster describing ONCR-719, previously known as ONCR-GBM, include:

Minimal expression of HSV-1 virus entry receptor, NECTIN-1, on human GBM samples suggests targeted oncolytic viruses are required to effectively treat human GBM tumors.
ONCR-719 has been engineered to enter tumor cells using either EGFR/EGFRvIII or NECTIN-1 as an entry receptor, thereby increasing virus tropism for GBM tumors.
EGFR-targeting and engineered fusogenic mutations in ONCR-719 enhance virus spread and tumor immunogenicity by driving syncytia formation in human GBM tumor cell lines.
ONCR-719 is engineered to include IL-12, an anti-PD-1 nanobody, 15-hydroxyprostaglandin dehydrogenase (HPGD), and a novel macrophage modulating-Fc enhanced antibody. These payloads confer enhanced T cell recruitment and activation and target the immune suppressive macrophages and myeloid cells in the tumor microenvironment. Multiple payloads or transgenes were screened using in vivo orthotopic GBM models to identify immune-modulatory payloads to target the GBM microenvironment.
Together, EGFR/EGFRvIII targeting, oncolytic potency, and incorporation of rationally designed payloads within ONCR-719 leads to enhanced anti-tumor efficacy and complete responses in preclinical orthotopic GBM models.
ONCR-719 is engineered for safety in the central nervous system using multiple CNS-specific microRNA targets, Oncorus’ clinically proven strategy to limit viral replication in healthy cells. When injected intracranially in an HSV-1 sensitive mouse, ONCR-719 demonstrates a greater than 50,000-fold tolerability window compared to the unattenuated strain.
"Oncolytic viruses are well-positioned to treat this aggressive form of brain cancer. We are excited to share ONCR-719 as a cutting-edge preclinical candidate that is engineered to improve outcomes and can stimulate a productive and durable anti-tumor immune response across multiple mouse models following a single intratumoral injection," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "Most notably, we’ve enabled the virus to use EGFR for entry, which is expressed at high levels in GBM. Underscoring the importance of this advance is our data showing that the canonical entry receptor for HSV, NECTIN-1, is only minimally expressed in GBM cells, which arguably makes using EGFR for entry an essential capability for such an agent. By utilizing our clinically proven microRNA attenuation strategy, ONCR-719 is engineered to protect healthy brain tissue while replicating at its full potential in tumor cells."

"GBM is the most common type of primary brain tumor in adults; it’s a devastating disease that has a great unmet need with a 5-year overall survival of approximately 7 percent," said Tooba Cheema, Ph.D., Senior Director, Translational Medicine and ONCR-719 Program Leader at Oncorus. "We engineered ONCR-719 to overcome the common impediment that this treatment class faces, limited spread of virus in the highly immunosuppressive GBM tumor microenvironment. We are pleased with the results demonstrated in preclinical models and look forward to seeing how our innovations translate into improved outcomes for GBM patients."

ONCR-719 is the company’s second candidate from its HSV Platform and is developed from a clinical isolate of HSV-1 selected for oncolytic potency across cancer cell lines. Further development of ONCR-719 is dependent on a strategic partnership or additional financing.

On November 18, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA) reported that its ongoing rolling Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) for lifileucel is expected to be completed in the first quarter of 2023 (Press release, Iovance Biotherapeutics, NOV 18, 2022, View Source [SID1234624239]).

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As part of an amendment to the ongoing investigational new drug application (IND) submitted during the third quarter of 2022, Iovance received recent FDA feedback regarding supplemental assay validation information and comparability data for lifileucel. Iovance will address these FDA comments promptly and will now complete its rolling BLA submission during the first quarter of 2023.

Lifileucel is an investigational tumor infiltrating lymphocyte (TIL) therapy for patients with advanced (unresectable or metastatic) melanoma who progressed on or after prior anti-PD-1/L1 therapy, and targeted BRAF/MEK inhibitor therapy where appropriate. There are no FDA approved therapies in this treatment setting.

Frederick Vogt, Ph.D., J.D., Iovance’s Interim President and Chief Executive Officer stated, "We continue to make substantial progress with our ongoing BLA submission and remain close to the finish line. The FDA has provided recent valuable feedback to the IND application and remains supportive during the rolling BLA submission process. Iovance is fully committed to securing FDA approval as soon as possible to deliver the first individualized, one-time cell therapy for advanced melanoma patients, who have a significant unmet medical need."

As previously announced, Iovance held a successful pre-BLA meeting in July 2022, and the rolling BLA commenced in August 2022. A rolling BLA allows Iovance to submit portions of the BLA to the FDA on an ongoing basis, which enables the FDA to begin review as early as possible as documents are received. The rolling BLA submission and eligibility for priority review are benefits available under the FDA’s guidance on expedited programs for serious conditions. The FDA previously granted a regenerative medicine advanced therapy (RMAT) designation for lifileucel in advanced melanoma.

The BLA submission for lifileucel is supported by positive clinical data from the C-144-01 clinical trial in patients with advanced melanoma. The Phase 3 trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma, on track to begin in late 2022, is intended to serve as a confirmatory study and is expected to be well underway at the time of a potential approval.

Investor Webcast on Friday, November 18, 8:00 a.m. ET

Iovance will host a webcast on Friday, November 18 at 8:00 a.m. ET to discuss this corporate update. To participate in the webcast, please register at https://register.vevent.com/register/BI99a18daf00f04087b70d9c6b45008d6f. The live webcast and replay can be accessed in the Investors section of the company’s website at IR.Iovance.com.

On November 18, 2022, Iovance Biotherapeutics reported that entered into a new Open Market Sale Agreement (the "Sales Agreement") with Jefferies LLC ("Jefferies") with respect to an at the market offering program, under which the Company may, from time to time in its sole discretion, issue and sell through Jefferies, acting as sales agent, up to $500.0 million of shares of the Company’s common stock, par value $0.000041666 per share (the "Common Shares") (Filing, 8-K, Iovance Biotherapeutics, NOV 18, 2022, View Source [SID1234624238]). The Prior Sales Agreement (as defined below) was terminated, and the Sales Agreement replaces the Prior Sales Agreement.

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The issuance and sale, if any, of the Common Shares by the Company under the Sales Agreement will be made pursuant to a prospectus supplement, dated November 18, 2022, to the Company’s registration statement on Form S-3ASR, originally filed with the Securities and Exchange Commission on May 27, 2020, which became effective immediately upon filing.

Pursuant to the Sales Agreement, Jefferies may sell the Common Shares by any method permitted by law deemed to be an "at the market" offering as defined in Rule 415 of the Securities Act of 1933, as amended (the "Securities Act"). Jefferies will use commercially reasonable efforts consistent with its normal trading and sales practices to sell the Common Shares from time to time, based upon instructions from the Company (including any price or size limits or other customary parameters or conditions the Company may impose).

The Company will pay Jefferies a commission of up to 3.0% of the gross sales proceeds of any Common Shares sold through Jefferies under the Sales Agreement.

The Company is not obligated to make any sales of Common Shares under the Sales Agreement. The offering of Common Shares pursuant to the Sales Agreement will terminate upon the earlier to occur of (i) the issuance and sale, through Jefferies, of all Common Shares subject to the Sales Agreement and (ii) termination of the Sales Agreement in accordance with its terms.

The Sales Agreement contains representations, warranties and covenants that are customary for transactions of this type. In addition, the Company has agreed to indemnify Jefferies against certain liabilities, including liabilities under the Securities Act and the Securities Exchange Act of 1934, as amended.

The foregoing description of the Sales Agreement is not complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference.

The legal opinion of DLA Piper LLP (US) as to the legality of the Common Shares is being filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation or sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.