On June 15, 2023 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has issued a partial clinical hold pausing new patient enrollment in UP-NEXT and UPGRADE-A, the company’s ongoing clinical trials of UpRi in platinum-sensitive ovarian cancer (Press release, Mersana Therapeutics, JUN 15, 2023, View Source [SID1234632729]). UPLIFT, Mersana’s ongoing clinical trial of UpRi in platinum-resistant ovarian cancer, completed enrollment in October 2022. Patients who are already enrolled in these trials may continue receiving UpRi. Mersana expects to lock its UPLIFT clinical trial database and disclose UPLIFT top-line data by early August.

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The partial clinical hold follows a submission by Mersana of a recent aggregate safety report of all patients dosed with UpRi (approximately 560 patients) evaluating bleeding events. As noted in FDA guidance, aggregate analyses generally become more informative as a drug progresses through development and accumulates data. Detection of a clinically meaningful risk, particularly in single-arm clinical trials, typically requires a large safety database to detect differences in rates of adverse events compared to those that are expected in the population being studied.

Although data on the background rate of bleeding in platinum-resistant ovarian cancer are limited, Mersana’s recent assessment determined that serious bleeding events appear to occur at a higher rate than background. While most bleeding cases in this aggregate safety analysis were low-grade, five (<1%) Grade 5 (fatal) bleeding events were observed among the approximately 560 patients dosed to date. The causes of bleeding events remain under investigation.

"Patient safety is always at the forefront for us, and work is now underway to compile further analyses that may inform FDA," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "Additionally, with UPLIFT top-line data on the near-term horizon, we will soon have a much more complete assessment of both the efficacy and safety profile for UpRi in platinum-resistant ovarian cancer."

The company is awaiting the FDA’s written correspondence regarding the partial clinical hold and expects the FDA will request a comprehensive assessment of UpRi safety data, inclusive of bleeding events. In addition, Mersana plans to submit to the FDA the UPLIFT safety and efficacy data once available. The company plans to seek alignment with the FDA to lift the partial clinical hold and resume enrollment in UP-NEXT and UPGRADE-A.

On June 15, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that the first patient was recently randomized in TILVANCE-301, a global, multicenter, registrational Phase 3 trial comparing Iovance TIL therapy lifileucel in combination with pembrolizumab versus pembrolizumab monotherapy in frontline advanced (unresectable or metastatic) melanoma (Press release, Iovance Biotherapeutics, JUN 15, 2023, View Source [SID1234632727]).

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Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "Our strategy is to offer TIL therapy across all lines of treatment for patients with advanced melanoma. Randomizing the first patient in TILVANCE-301, our first Phase 3 trial at Iovance, is an important milestone. The trial offers TIL therapy as part of an earlier treatment approach for frontline advanced melanoma, while serving as a confirmatory trial to convert an accelerated approval to full approval for lifileucel in post-anti-PD-1 melanoma. TILVANCE-301 is expected to be well underway at the time of potential accelerated approval in this initial indication. This trial may also provide important insights into the Iovance platform approach for TIL and anti-PD-1 therapy combinations in additional solid tumors."

TILVANCE-301 builds on Iovance clinical data and decades of experience at the National Cancer Institute (NCI) on the use of TIL therapy in early line advanced melanoma patients. An oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2021 highlighted positive results for Iovance TIL therapy in combination with pembrolizumab in patients with advanced melanoma, cervical and head and neck cancers who were naïve to prior anti-PD-1 therapy. In April 2022, Iovance announced updated positive results demonstrating a 67% ORR and durability of response for lifileucel in combination with pembrolizumab in advanced melanoma from Cohort 1A of the IOV-COM-202 trial, which have remained consistent in nearly 20 patients treated to date.

The U.S. Food and Drug Administration (FDA) previously agreed that dual primary endpoints of objective response rate (ORR) and progression free survival (PFS) in TILVANCE-301 can support accelerated and full approvals of lifileucel in frontline advanced melanoma. The FDA also agreed that TILVANCE-301, which is expected to be well underway at the time of a potential accelerated approval of lifileucel in post-anti-PD-1 melanoma, can serve as the confirmatory trial for full approval in this initial indication. The FDA granted Priority Review for lifileucel in post-anti-PD-1 melanoma and assigned November 25, 2023, as the target action date for a decision under the Prescription Drug User Fee Act (PDUFA).

About TILVANCE-301
TILVANCE-301 will randomize approximately 670 patients to investigate the safety and efficacy of lifileucel in combination with pembrolizumab (experimental arm) compared with pembrolizumab monotherapy (control arm). Trial sites are actively enrolling adult participants with unresectable or metastatic melanoma who have not received prior therapy for advanced disease. Participants randomized to the control arm who experience disease progression may be treated with lifileucel monotherapy in an optional crossover period. For more information, eligibility criteria, and trial locations, please visit www.clinicaltrials.gov (NCT05727904) or contact [email protected].

On June 15, 2023 MEI Pharma, Inc. (Nasdaq: MEIP) ("MEI"), a clinical-stage pharmaceutical company focused on advancing new therapies for cancer, and Infinity Pharmaceuticals, Inc. (Nasdaq: INFI) ("Infinity"), a clinical-stage biotechnology company developing eganelisib, a first-in-class, oral, immuno-oncology macrophage reprogramming drug candidate, reported that the companies will host a recorded joint video webcast that will be available at 8:00 am Eastern Time on June 19, 2023 (Press release, Infinity Pharmaceuticals, JUN 15, 2023, View Source [SID1234632726]). On the webcast Mr. David Urso will provide an update on the pending merger and an overview of the combined company, which joins the expertise and resources of MEI and Infinity to advance a robust pipeline of three clinical-stage oncology drug candidates.

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In addition to presentations from the executive management from MEI and Infinity on the three programs, the webcast includes commentary and discussion with Dr. Ezra Cohen, a recognized expert in the treatment of squamous cell carcinoma of the head & neck (SCCHN) and recently the Chief, Division of Hematology-Oncology, and Associate Director of Clinical Science at UC San Diego Moores Cancer Center. Following the prepared presentations, Dr. Nick Abbott, most recently the senior sell side biotech analyst at Wells Fargo Securities will ask questions of the presenters, Dr. Robert Ilaria, Dr. Ezra Cohen and Dr. Richard Ghalie.

The combined company’s development pipeline consists of three differentiated programs. All three clinical-stage development programs have the potential, in combination with current therapies, to overcome known resistance mechanisms and meaningfully improve patient outcomes:

Eganelisib, an oral immuno-oncology macrophage reprogramming product candidate, which is planned to be evaluated in combination with the PD-1 targeted checkpoint inhibitor pembrolizumab (KEYTRUDA) in patients with head and neck squamous cell carcinoma (HNSCC);
Voruciclib, an oral CDK9 inhibitor, currently being studied in combination with venetoclax (VENCLEXTA) in patients with hematologic malignancies; and
ME-344, a novel tumor selective mitochondrial inhibitor targeting the OXPHOS pathway, to be evaluated in combination with bevacizumab (AVASTIN) in patients with relapsed colorectal cancer.
Video Webcast Information

You can access the video webcast under the investor relations section of MEI’s website on the "Events and Presentation" page at www.meipharma.com, or under the investor relations page of Infinity’s website on its "Events and Presentation" page at www.infi.com. The pre-recorded video webcast will be archived for at least 30 days after the conclusion of the event.

On June 15, 2023 GlycoMimetics, Inc. (Nasdaq: GLYC) a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers and inflammatory diseases, reported that the U.S. Food and Drug Administration (FDA) cleared the addition of a protocol amendment to the company’s pivotal Phase 3 study of uproleselan for relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) (Press release, GlycoMimetics, JUN 15, 2023, View Source [SID1234632725]). The amendment will allow a time-based analysis of the primary endpoint of overall survival to be conducted following a defined cutoff date if the 295 survival events originally planned for an event driven analysis have not been observed. With the addition of a time-based analysis, topline results are expected to be reported by the end Q2 2024.

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"We are pleased the FDA cleared the addition of a time-based pathway to final analysis as it provides the opportunity to evaluate the effect of uproleselan on R/R AML based on a clinically mature database with more than three years median follow-up," said Harout Semerjian, Chief Executive Officer of GlycoMimetics. "This approach is consistent with regulatory precedent adopted for a prior pivotal AML study for an approved drug and reflects our commitment to science-driven analysis as we seek to deliver uproleselan to R/R AML patients in need of new treatment options as soon as possible."

The Phase 3 trial completed enrollment of 388 patients across 70 sites in nine countries in November 2021. An event based final analysis of overall survival was previously expected after year end 2022, but the number of events has slowed, resulting in the projected timeline being extended.

Based on blinded pooled data observed to date, a time-based final analysis in Q2 2024 is expected to yield a clinically mature dataset to evaluate uproleselan in R/R AML. This dataset is expected to reflect a median follow-up of greater than three years, including at least two years of post-transplant data. The majority of surviving patients in the study received hematopoietic stem cell transplantation (HSCT). As a result, the company believes the capture rate of survival events for this study beyond Q2 2024 would provide limited additional value for the primary analysis.

Two years post-transplant is generally considered an important milestone in AML because most patients who survive at least two years post-transplant without experiencing disease relapse are typically deemed to be long-term survivors. For patients over two years post-transplant, disease relapse is less likely.1

As part of the protocol amendment, the FDA also cleared the addition of landmark EFS and overall survival analyses as secondary endpoints.

About Uproleselan

Discovered and developed by GlycoMimetics, uproleselan is an investigational first-in-class, E-selectin antagonist. Uproleselan (yoo’ pro le’se lan), currently in a comprehensive Phase 3 development program in acute myeloid leukemia (AML), has received Breakthrough Therapy and Fast Track designations from the U.S. FDA and Breakthrough Therapy designation from the Chinese National Medical Products Administration for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin binding and stimulation of myeloid cells. E-selectin is expressed on the surface of blood vessels, and its binding to myeloid cells confers a pro-survival effect. Uproleselan intends to provide a novel approach to disrupting established mechanisms of leukemic cell resistance.

On June 15, 2023 Flamingo Therapeutics ("Flamingo") reported that it has been awarded a research grant of €1.7 million by Flanders Innovation & Entrepreneurship (VLAIO) (Press release, Flamingo Therapeutics, JUN 15, 2023, View Source;utm_medium=rss&utm_campaign=flamingo-therapeutics-receives-e1-7m-grant-award-from-vlaio-to-advance-rna-targeting-oncology-portfolio [SID1234632724]). The award represents the funding at 60% of a €2.9 million project. Funding from the grant will be used to advance Flamingo’s RNA-targeting oncology portfolio, including translational research for its lead clinical program, danvatirsen in Phase II in head and neck squamous cell carcinoma, and preclinical work on its long non-coding RNA (LncRNA) program targeting MALAT-1.

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"We are thrilled to be recognized by VLAIO as a company who is innovating and disrupting the oncology landscape with our RNA-targeting approach," said Floor Stam, Head of Corporate Development and Operations. "This award provides further validation of our approach in creating a meaningful pipeline of programs that target undruggable transcription factors and non-coding RNA, such as STAT3 and MALAT-1. We thank VLAIO for their partnership and collaboration in helping us build a leading oncology company based on RNA therapeutics."

Danvatirsen is an antisense oligonucleotide (ASO) that selectively targets STAT3 and has shown clinical activity in two Phase II clinical studies. Danvatirsen binds to STAT3 mRNA, inducing breakdown of the transcript. Currently, danvatirsen is planned to continue Phase 2 clinical development for head and neck squamous cell carcinoma to advance the program through key clinical milestones and data readouts. Flamingo is also advancing FTX-001, Flamingo’s most advanced long non-coding RNA (LncRNA) program which targets MALAT-1, through readiness for Phase 1 in solid tumors. LncRNAs are a large and untapped class of disease-causing targets within the "dark matter" of the human genome.

Receipt of this funding follows the merger between Flamingo and Dynacure, announced in March 2023.

About VLAIO
Flanders Innovation & Entrepreneurship (Agentschap Innoveren & Ondernemen – VLAIO) is a Flemish Government agency that stimulates and supports R&D activities by innovative entrepreneurs and companies. More information: View Source