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Iovance Biotherapeutics Announces First Patient Randomized in Phase 3 TILVANCE-301 Trial in Frontline Advanced Melanoma

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].

MEI Pharma and Infinity Pharmaceuticals Host Video Webcast Providing Overview and Update on Pending Merger to Advance Three Promising Clinical Oncology Candidates

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.

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.

GlycoMimetics Announces U.S. Food and Drug Administration Clears Addition of Time-based Final Analysis to Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory Acute Myeloid Leukemia

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.

"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.

Flamingo Therapeutics Receives €1.7M Grant Award from VLAIO to Advance RNA-Targeting Oncology Portfolio

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.

"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

Corvus Pharmaceuticals Presents New CPI-818 Interim Data at the International Conference on Malignant Lymphoma

On June 15, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported new data for CPI-818, the Company’s ITK inhibitor, demonstrating the potential to treat a variety of solid and hematological cancers based on a novel immunotherapy mechanism of action (Press release, Corvus Pharmaceuticals, JUN 15, 2023, View Source [SID1234632723]). The data includes updated interim results from the CPI-818 Phase 1/1b clinical trial that continues to demonstrate the potential of ITK inhibition and the absolute lymphocyte count (ALC) biomarker in T cell lymphoma (TCL). The data is being presented in a poster at the International Conference on Malignant Lymphoma (ICML) meeting, which is taking place June 13-17, 2023 in Lugano, Switzerland.

"The CPI-818 data presented at the ICML meeting demonstrates the potential of ITK inhibition to provide a novel immunotherapy mechanism of action for cancer therapy," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "The preclinical and clinical data indicate a consistent and comprehensive rationale based on the biology and mechanism of immune enhancement resulting from selective ITK inhibition. This includes the ability to modulate normal T cell differentiation to enhance and strengthen the immune system’s ability to treat lymphomas and solid tumors. We see this in the interim tumor response data, which showed that a majority of the patients treated with the optimal dose of 200mg twice per day of CPI-818 experience tumor regression. As we consider the landscape of cancer therapy targets, ITK is not in the category of immune checkpoints, but rather it is a kinase that controls whether T cells become cancer killing cells or inflammatory cells. This positioning and the supporting research provide a strong foundation for the continued development of CPI-818 as a monotherapy and its future use in combinations with other therapies. We are excited to build upon these results and plan to meet with the U.S. FDA in the third quarter 2023 to discuss a potential registrational Phase 3 clinical trial for CPI-818 in T cell lymphoma. We also have begun planning for clinical trials with CPI-818 monotherapy in solid tumors. Overall, we have increasing confidence that CPI-818, if approved, can be a novel backbone for various immunotherapies of cancer."

CPI-818 Data Presented at ICML
The CPI-818 preclinical and clinical data was presented by Ning Ding, Ph.D. from Peking University Cancer Hospital & Institute in Beijing, China, in a poster session (abstract #193) today at the ICML meeting. The poster is available to ICML attendees in the poster hall and e-poster gallery, is also available on the Publications and Presentations page of the Corvus website. The key highlights from the poster presentation include:

Phase 1/1b Clinical Trial Interim Data
CPI-818 is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. Corvus recently incorporated a minimum ALC as an eligibility criterion for enrollment in the clinical trial. Based on the current enrollment rate of the Phase 1/1b clinical trial, Corvus believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registrational Phase 3 randomized clinical trial. As recommended by the FDA, Corvus plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place during the third quarter of this year.

Updated interim data as of May 18, 2023 (waterfall plot shown below): A total of 30 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose, including 20 evaluable for tumor response. There were 3 complete responses (CR) and 3 partial responses (PR) with one of these PRs demonstrating continued regression of the tumor. One of the patients with a CR and 2 with PRs remained on therapy. A total of ten patients remained on therapy, including six who have not had their initial tumor response evaluation. For patients with ALC above 900 per cubic milliliter of blood, objective responses (CR plus PR) were seen in 6 of 14 patients with disease control (CR, PR and stable disease) in 12 of 14 patients. No objective responses were seen in six patients (0 for 6) with ALC below 900.
Updated interim data as of May 18, 2023: In one TCL patient treated with CPI-818 for which serial tumor biopsy samples could readily be obtained, single cell RNA sequencing from paired samples comparing baseline and on-treatment specimens showed an increase in tumor infiltrating CD8+ T cells; an increase in cytolytic effector molecules such as granzymes and perforin in the T cells; and an increase in T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells. In addition, flow cytometry analysis of paired blood samples comparing baseline and on treatment revealed a similar finding in both CD8 T cells and CD4 T cells. These results are consistent with preclinical data described below and support the novel immunotherapy mechanism of action of selective ITK inhibition, which is based on Th1 skewing and the resulting shift in immune response to eliminating cancer cells. Additional laboratory findings indicated that treatment with CPI-818 induces a reversal of T cells expressing exhaustion markers. T cell exhaustion is a known mechanism of resistance to checkpoint inhibitor therapy.
Figure 1: Waterfall Plot for Patients in the 200 mg Dose Cohort of the CPI-818 Phase 1/1b Clinical Trial for T Cell Lymphoma. The plot shows the best percent change in tumor volume in the 18 patients (out of 20 total evaluable patients) that were measurable by CT scan. The two other patients had cutaneous and blood involvement; one was a patient with a PR and one patient had progression.

The plot shows the best percent change in tumor volume in the 18 patients (out of 20 total evaluable patients) that were measurable by CT scan. The two other patients had cutaneous and blood involvement; one was a patient with a PR and one patient had progression.

Preclinical Data Supporting CPI-818’s Novel Immunotherapy Mechanism of Action
ITK inhibition with CPI-818 has the potential to treat solid and hematological cancers through a novel mechanism of action that has demonstrated the ability to modulate T cell differentiation and enhance the anti-tumor immune response via Th1 skewing, increased T cell cytolytic capacity and reduction of T cell exhaustion.

CPI-818 monotherapy provided statistically significant inhibition of tumor growth in established tumors in the following cancer models: EL4 TCL, A20 B cell lymphoma and CT26 colon cancer.
In the EL4 TCL model, treatment with CPI-818 led to increased infiltration of normal CD8+ T cells into the tumor. In addition, these CD8+ T cells had higher expression of perforin, an effector molecule produced by killer T cells that is involved in killing cancer cells.
In the CT26 colon cancer model, the depletion of CD8 cells reduced the efficacy of CPI-818 treatment, indicating that its mechanism of action involves the production of normal CD8+ T cells.
In the CT26 colon cancer model, treatment with CPI-818 reduced the expression of T cell exhaustion markers. T cell exhaustion is a phenomenon seen in tumors and chronic infections where prolonged exposure to antigens results in exhausted or ineffective T cell function and inability to eliminate tumors or infections.
In other murine studies using antigen primed T cells that were repeatedly stimulated, CPI-818 reduced the development of T cell exhaustion and reversed it in already exhausted T cells. These reinvigorated T cells regained their cancer cell killing capacity.
These findings indicate that the inhibition of ITK by CPI-818 produces changes in the tumor microenvironment that enhance anti-tumor immunity creating a less favorable environment for tumor growth.