On September 9, 2022 EORTC reported that Important new results from trials will be presented at this year’s ESMO (Free ESMO Whitepaper) conference starting tomorrow (October 9) in Paris (Press release, EORTC, SEP 9, 2022, https://www.eortc.org/blog/2022/09/09/new-results-updates-and-forthcoming-eortc-trials-in-melanoma-soft-tissue-sarcoma-head-and-neck-testicular-and-lung-cancer-presented-at-esmo-2022/ [SID1234619321]). Once again, immunotherapy – the use of drugs that stimulate the immune system so that it can find and attack cancer cells – plays a leading role, as do studies into patients’ quality of life.

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Professor Alexander Eggermont will present results from the randomized phase III double-blind EORTC 1325/KEYNOTE-054 trial 1 of the immunotherapy pembrolizumab vs placebo in 1019 patients who had had their high-risk stage III melanomas surgically removed. Between August 2015 and November 2016, patients were given either 200 mg of immunotherapy or a placebo every three weeks until disease recurrence or unacceptable toxicity was observed. At five years’ media follow-up, the researchers found that recurrence-free survival, distant metastasis-free survival, and the time from randomization until a second disease recurrence, progression of the first recurrence, or death, were all significantly improved in the patients who had received the active treatment.

A second analysis of the trial results 2 centered on the effect of pembrolizumab on patients’ quality of life. The researchers found that there were no clinically relevant differences in long-term quality of life between the active treatment and the placebo arm. Differences related to physical functioning, role, emotional, cognitive, and social functioning, and fatigue were insignificant, and neither were immune-related adverse events associated with any clinically relevant changes.

A further study of pembrolizumab, this time in early-stage non-small cell lung cancer, will be presented by Professor Solange Peters 3. The PEARLS/KEYNOTE-091 study investigated the effect of pembrolizumab on patients who had had complete surgical resection of stage IB to IIIA tumors. The further analysis presented at ESMO (Free ESMO Whitepaper) focused on a sub-group of patients who had increased levels of PD-L1, a protein that allows cancer cells to evade the immune system. Earlier results from the trial had appeared to show that pembrolizumab had little benefit in patients with high levels of PD-LI, but further, more detailed analysis showed that disease-free survival in those patients with the highest levels of the protein was improved. The lack of statistically significant benefit for these patients in the earlier analysis most likely results from placebo overperformance, the need for a longer follow-up, and smaller population size. But in any event, the data support the benefit of the treatment for all stage IB to IIIA resected patients, regardless of PD-LI expression, the researchers say.

The EORTC has an important track record in the development and use of Quality of Life (QoL) measurement instruments in clinical trials. Studies usually focus on radiological and survival endpoints with QoL as a supplementary endpoint, but for older patients, it is known that QoL rather than length of life is increasingly important. Evidence on optimal treatments in the elderly with metastatic soft tissue sarcoma is limited, yet patients understandably want to have relevant information before making the decision to start palliative treatment. Therefore a new clinical trial 4, ‘EORTC 1976 TOLERANCE’, for this specific group of metastatic elderly rare cancer patients has been designed with significant input from patients. The study design will be presented by Professor Winette van der Graaf, EORTC President, and study coordinator. In the randomized three-arm study the primary endpoint will be QoL, particularly self-reported physical and role functioning at 12 weeks. In the trial, standard three-weekly doxorubicine will be compared to metronomic (the frequent administration of low dose) schedules of doxorubicin or cyclophosphamide. Patients older than 70, or between 65 and 69 years of age with a G8 score of 14 or less with progressive metastatic soft tissue sarcoma will be entered into the study. A total of 185 patients will be needed to get an answer as to whether metronomic doxorubicin or cyclophosphamide leads to a lower burden in terms of physical and role functioning than the standard doxorubicin schedule.

Also in soft tissue sarcoma, Dr. Georgios Kantidakis, on behalf of the EORTC Soft Tissue and Bone Sarcoma Group, will present new benchmarks for designing clinical trials in advanced metastatic liposarcoma (LPS) and synovial sarcoma (SS) 5. The researchers carried out a meta-analysis to update reference values for phase II soft tissue sarcoma (STS) trials. The information studied included 1030 LPS patients in 25 trials as well as 348 SS patients in 13 trials. Study endpoints were progression-free survival rates at three and six months. The researchers conclude that minimum values in patients receiving first-line therapy are 79% at three months and 69% at six months in LPS, and 82% and 69% respectively for SS. For patients who have already received treatment, recommended progression-free survival rates at three and six months, suggesting drug activity, are 63% and 44% respectively for LPS, and 60% and 41% for SS. These new benchmarks will help better design future trials, the researchers believe.

Dr. Silke Gillessen will present the results of an EORTC analysis of the International Germ Cell Cancer Collaborative Group (IGCCCG) Update database 6. In stage I testicular cancer, active surveillance after orchiectomy (the surgical removal of a testicle) is the preferred management in many patients. However, it is associated with a 15 to 30% relapse rate. The researchers identified all patients with metastatic gonadal germ cell tumors for whom they had complete information on the initial tumor stage, and compared the outcomes of patients relapsing from clinical stage I (CSI) disease to those with de novo metastatic disease. They found no difference progression-free survival or overall survival in patients relapsing from their original CSI as compared with de novo metastatic disease when adjusted for their prognostic group, though a substantial proportion of CSI patients relapsed with intermediate or poor prognostic features in need of intensified treatment. The study underlines the importance of performing active surveillance well in order to detect recurrence in CSI patients as early as possible, say the researchers.

Professor Christian Simon will present the design of an EORTC randomized controlled trial to assess the effect of either surgery or radiotherapy for early-stage oropharyngeal, supraglottic, and hypopharyngeal cancers on the recovery of these head and neck cancer patients’ ability to swallow 7. Both are generally effective at controlling tumor growth but have different side effects, and choice is generally based on the choice of the individual patient and/or institution. Recently the introduction of new surgical and radiotherapeutic techniques has led to an improvement in side effects resulting from treatment. The Phase III trial will enroll 112 patients from 29 European centers, and recruitment had already reached the halfway mark in January 2022. The researchers hope that it will provide a conclusive answer to the question and therefore provide a robust basis for the choice of treatment.

Dr. Jordi Remon, on behalf of the EORTC Lung Cancer Group, will report the results of a clinical trial (APPLE trial-EORTC 1613) 8. This trial supports the hypothesis that among patients with advanced non-small cell lung cancer and epidermal growth factor (EGFR) mutation treated with first-generation EGFR tyrosine kinase drugs, plasma assessment (liquid biopsy) is feasible to detect the mutation of resistance (T790M) to this treatment before radiological progression. This enables personalized treatment to start earlier. In the trial, patients from six countries were enrolled in three arms, results from two of which were presented at ESMO (Free ESMO Whitepaper). Patients in Arm B were given the EGFR inhibitor gefitinib until the emergence of T790M in a liquid biopsy or progression of their disease, whereupon they were treated with the targeted therapy osimertinib. In Arm C, the internal control arm, patients received gefitinib until progression and then osimertinib. Median follow-up was 30 months. The researchers found that monitoring of T790M status in plasma gave a good indication of molecular progression before further symptoms appeared, and led to an earlier switch to osimertinib in 17% of patients with satisfactory outcomes in progression-free and overall survival.

Abstract 804P – Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: 5-year results of the EORTC 1325-MG/Keynote-054 double-blinded phase III trial
Abstract LBA44 – Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: long-term quality of life analysis results of the EORTC 1325-MG/Keynote-054 double-blinded phase 3 trial
Abstract 930MO – PD-L1 expression and outcomes of pembrolizumab and placebo in completely resected stage IB-IIIA NSCLC: Subgroup analysis of PEARLS/KEYNOTE-091
Abstract 1526TiP – TOLERANCE: An EORTC STBSG-QLG-ETF 3-arm randomized study on health-related quality of life of elderly patients with advanced soft tissue sarcoma undergoing doxorubicin alone three weekly or doxorubicin weekly or cyclophosphamide plus predniso(lo)ne treatment
Abstract 1491MO – New benchmarks for designing clinical trials in advanced or metastatic liposarcoma (LPS) or synovial sarcoma (SS): An EORTC soft tissue and bone sarcoma group meta-analysis
Abstract 512MO – Outcomes of relapsed clinical stage I versus de novo metastatic testicular cancer patients: An analysis of the IGCCCG Update database
Abstract 706TiP – Phase III study assessing the "best of" radiotherapy compared to the "best of" surgery (trans-oral surgery (TOS)) in patients with T1-T2, N0-N1 oropharyngeal, supraglottic carcinoma and with T1, N0 hypopharyngeal carcinoma
Abstract LBA51 – Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial

On September 9, 2022, Plus Therapeutics, Inc. (the "Company") reported that entered into an Equity Distribution Agreement (the "Distribution Agreement") with Canaccord Genuity LLC (the "Agent"), pursuant to which the Company may issue and sell, from time to time, shares of its common stock having an aggregate offering price of up to $5,000,000 (the "Shares"), depending on market demand, with the Agent acting as an agent for sales (Filing, 8-K, Cytori Therapeutics, SEP 9, 2022, View Source [SID1234619320]). Sales of the Shares may be made by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415(a)(4) of the Securities Act of 1933, as amended (the "Securities Act"), including, without limitation, sales made directly on or through the NASDAQ Capital Market. The Agent will use its commercially reasonable efforts to sell the Shares requested by the Company to be sold on its behalf, consistent with the Agent’s normal trading and sales practices, under the terms and subject to the conditions set forth in the Distribution Agreement. The Company has no obligation to sell any of the Shares. The Company may instruct the Agent not to sell the Shares if the sales cannot be effected at or above the price designated by the Company from time to time and the Company may at any time suspend sales pursuant to the Distribution Agreement.

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The Company will pay the Agent a commission of up to 3.0% of the gross proceeds from the sale of Shares by the Agent under the Distribution Agreement. The Company has also agreed to reimburse the Agent for its reasonable documented out-of-pocket expenses, including fees and disbursements of its counsel, in the amount of $50,000. In addition, the Company has agreed to provide customary indemnification rights to the Agent.

The Offering will terminate upon the earlier of (1) the issuance and sale of all shares of the Company’s common stock subject to the Distribution Agreement, or (2) the termination of the Distribution Agreement as permitted therein, including by either party at any time without liability of any party.

Any sales of Shares under the Distribution Agreement will be made pursuant to the Company’s Registration Statement on Form S-3 (File No. 333-249410), including the related prospectus, filed with the Securities and Exchange Commission (the "SEC") on October 9, 2020 and declared effective on October 19, 2020, as supplemented by the prospectus supplement dated September 9, 2022, and any applicable additional prospectus supplements related to the Offering that form a part of the Registration Statement. The aggregate market value of Shares eligible for sale in the Offering and under the Distribution Agreement will be subject to the limitations of General Instruction I.B.6 of Form S-3, to the extent required under such instruction. The Company intends to use the net proceeds from this offering for general corporate purposes and for working capital.

The foregoing description of the Distribution Agreement does not purport to be complete and is qualified in its entirety by reference to the Distribution Agreement, which is filed as Exhibit 1.1 to this report and is incorporated herein by reference. A copy of the legal opinion of Hogan Lovells US LLP regarding the legality of the issuance and sale of the Shares is filed as Exhibit 5.1 to this report and is incorporated by reference herein.

This Current Report on Form 8-K does not constitute an offer to sell or the solicitation of an offer to buy any Shares, nor shall there be any offer, solicitation or sale of any Shares, in any jurisdiction in which it is unlawful to make the offer, solicitation or sale.

On September 9, 2022 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that positive follow-up data from its ongoing first-in-human Phase 1/2 trial evaluating the safety and efficacy of the Company’s novel CAR-T cell therapy candidate, BNT211, in patients with relapsed or refractory advanced solid tumors (Press release, BioNTech, SEP 9, 2022, View Source [SID1234619318]). The results demonstrated encouraging signs of anti-tumor activity and the safety profile remained manageable for the two tested dose levels. The data were presented in the Investigational Immunotherapy Proffered Paper Session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 by Prof. Andreas Mackensen, M.D., University Hospital Erlangen, Germany.

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BNT211 is a novel therapeutic approach which comprises a synergistic combination of two of BioNTech’s proprietary platforms. The candidate combines an autologous chimeric antigen receptor (CAR) T cell therapy targeting the oncofetal antigen Claudin-6 (CLDN6) with a CLDN6-encoding CAR-T cell amplifying RNA vaccine (CARVac). The product candidate recently received Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) for the third- or later-line treatment of testicular germ cell tumors. The designation was granted based on the encouraging initial data particularly in patients with testicular cancer which is the most common type of germ cell tumors. BioNTech presented data from the ongoing Phase 1/2 trial (NCT04503278; 2019-004323-20) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2022 and at the annual meeting of the Association for Cancer Immunotherapy (CIMT) (Free CIMT Whitepaper) in May 2022.

"This new dataset further supports the encouraging results we have seen for BNT211 to date. Together with the recently granted PRIME designation for BNT211 in testicular cancer it also reinforces our strategy to combine two of our key technology platforms in hard-to-treat tumor indications," said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. "We are grateful for the continued support from both clinicians and regulators that enables us to rapidly advance the clinical evaluation of BNT211 as a novel treatment option for cancer patients with an otherwise very poor prognosis."

The updated data read-out presented at ESMO (Free ESMO Whitepaper) (data cut-offs: June 15, 2022 for safety and August 16, 2022 for efficacy) included data from 22 patients (21 evaluable for efficacy) who received CLDN6 CAR-T cells at dose levels 1 (1×107 CAR-T cells, n=7, including one patient with CAR-T dose below dose level 1) and 2 (1×108 CAR-T cells, n=15) alone or combined with CARVac. Tumor indications included testicular cancer (n=13), ovarian cancer (n=4), endometrial cancer, fallopian tube cancer, sarcoma, gastric cancer (one patient each) and one patient with a tumor of unknown primary origin. Treatment with CLDN6 CAR-T alone or in combination with CARVac up to dose level 2 showed encouraging signs of clinical activity and was well tolerated. All 22 patients showed robust, dose-dependent CAR-T cell expansion after infusion with cell frequencies close to 109 total counts in dose level 2. At the cut-off date, available data demonstrated the long-term persistence of CAR-T cells observed in some patients for more than 100 days, and in one patient for 200 days. Two patients have been treated without lymphodepletion as preconditioning and a strongly reduced CAR-T expansion was observed. Adverse events, including cytokine release syndromes (CRS) and dose limiting toxicities were manageable. One transient occurrence of neurotoxicity grade 1 and one grade 3 CRS were observed that quickly resolved.

Efficacy assessment of the 21 evaluable patients showed a best overall response rate (ORR) of 33% and a disease control rate (DCR) of 67% with one complete response, six partial responses and seven patients with stable disease. In line with the earlier data set initially presented at AACR (Free AACR Whitepaper) this year, particularly encouraging clinical responses were seen in patients with testicular cancer treated with dose level 2 after lymphodepletion (n=7), where one complete response, three partial responses and two stable diseases were observed, representing an ORR of 57% and a DCR of 85%. As previously reported, antitumor activity tended to be higher at the higher dose of CAR-T cells and when combined with the mRNA vaccine. 5 of 10 patients in the CARVac combination group showed a partial response compared to 2 of 9 patients in the monotherapy cohort (CAR-T cell treatment only) excluding two patients that have been treated without lymphodepletion.

About BNT211
Aiming to harness the power of cell therapies for solid cancers and to overcoming hurdles to date, BioNTech has combined their CAR-T and FixVac platform technologies to develop a highly tumor-specific CAR-T cell therapy product which is consecutively enhanced by a CAR-T Cell Amplifying RNA Vaccine (CARVac) that is based on BioNTech’s mRNA-lipoplex technology and encodes for the respective CAR-T target antigen. CARVac is based on BioNTech’s backbone-optimized uridine mRNA (uRNA)-lipoplex technology which through its inherent adjuvant function enables a potent T cell stimulation to improve persistence and functionality of the adoptively transferred CAR-T cells, thereby enabling the investigation of a therapeutic effect even at low CAR-T doses. BNT211 is an investigational CAR-T cell therapy directed against the novel oncofetal antigen Claudin-6 (CLDN6), a target discovered by BioNTech founders and expressed on multiple solid tumors such as ovarian cancer, sarcoma, testicular cancer, endometrial cancer and gastric cancer. The program is currently being evaluated in a first-in-human Phase 1/2 trial as a monotherapy and in combination with a CLDN6-encoding CARVac, aiming to boost persistence and functionality of the CLDN6-CAR-T cells, in patients with CLDN6-positive relapsed or refractory advanced solid tumors.

On September 9, 2022, AIM ImmunoTech Inc. (the "Company") Presented a company presentation (Presentation, AIM ImmunoTech, SEP 9, 2022, View Source [SID1234619317]).

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On September 9, 2022 The board of directors of AbbVie Inc. (NYSE: ABBV) reported a quarterly cash dividend of $1.41 per share (Press release, AbbVie, SEP 9, 2022, View Source [SID1234619316]).

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The cash dividend is payable November 15, 2022, to stockholders of record at the close of business on October 14, 2022.

Since the company’s inception in 2013, AbbVie has increased its dividend by more than 250 percent. AbbVie is a member of the S&P Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.