On June 27, 2023 AVEO Oncology, an LG Chem company, ("AVEO"), announced today that it has completed enrollment in the pivotal Phase 3 TiNivo-2 study in patients with advanced relapsed or refractory renal cell carcinoma (RCC) following prior immunotherapy exposure. The study is evaluating FOTIVDA (tivozanib) in combination with OPDIVO (nivolumab), Bristol Myers Squibb’s anti-PD-1 immunotherapy. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for the treatment of adult patients with RCC following two or more prior systemic therapies.

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There are currently no National Comprehensive Cancer Network (NCCN) Category 1 recommended agents for patients with advanced RCC who were previously treated with prior immunotherapy. All currently available treatment options for advanced RCC were approved based on clinical studies conducted prior to the introduction of frontline immunotherapy combinations. There is an unmet need to improve the understanding of treatment sequencing and provide new treatment regimens for advanced RCC.

The randomized, controlled, open-label TiNivo-2 Phase 3 study enrolled patients with RCC who have progressed following prior immunotherapy treatment. Patients were randomized 1:1 to receive either low dose FOTIVDA in combination with OPDIVO or standard dose FOTIVDA alone. The TiNivo-2 study’s primary endpoint is progression free survival, with key secondary endpoints to include overall survival, overall response rate, duration of response and safety.

The TiNivo-2 study enrolled across clinical sites in the United States, Canada, Mexico, Europe and South America. "We are very excited to have achieved this interim milestone in the TiNivo-2 study and we are grateful to our global investigators, our AVEO development staff, and especially to the patients who are participating in the study. The TiNivo-2 study addresses an important question in the treatment of RCC, and we continue to work diligently to deliver the study results once data mature," said AVEO’s Chief Medical Officer, Dr. Martin Birkhofer.

"The TiNivo-2 study will provide us with a robust Phase 3 dataset to answer the outstanding question of whether adding a PD-1 Inhibitor (nivolumab) to a VEGF TKI (tivozanib), provides additional efficacy and acceptable safety over a single agent VEGF TKI following prior immunotherapy," said Toni Choueiri, M.D., Director, Lank Center for Genitourinary Oncology; Director, Kidney Cancer Center; Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute. "TiNivo-2 is a particularly important study for understanding appropriate sequencing strategies for RCC patients following immunotherapy given the presentation at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting of the CONTACT-03 study where adding a PD-L1 inhibitor (atezolizumab) to full dose cabozantinib failed to show a benefit over cabozantinib alone in RCC patients treated with prior immunotherapy."

The Company expects to share initial results from the TiNivo-2 study when the data mature, which is anticipated in the second half of 2024.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.4 FOTIVDA was discovered by Kyowa Kirin.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTION

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.AVEOoncology.com.

On June 27, 2023 Independent biopharmaceutical company Specialised Therapeutics (ST) reported that a new therapy to treat the most common type of non-Hodgkin lymphoma in adults – diffuse large B-cell lymphoma – is now approved for use in Australia (Press release, Specialised Therapeutics Asia, JUN 27, 2023, View Source [SID1234632939]).

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The Therapeutic Goods Administration (TGA) has provisionally approved MINJUVI (tafasitamab) "in combination with lenalidomide followed by MINJUVI monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT)".[1]

Australian lymphoma specialist and current chair of the Australasian Lymphoma Alliance, Professor Chan Cheah, said the MINJUVI approval was a great step forward for patients who had been diagnosed with DLBCL and relapsed, as the MINJUVI regimen provides an opportunity for longer-term disease management.

"I think it is great news for patients," Professor Cheah said. "We do have chemotherapy options and we cure about two-thirds of patients using that approach. Unfortunately, a substantial proportion of patients either don’t respond to chemotherapy, or the disease comes back after chemotherapy, and they need better treatments."

MINJUVI, a CD19-targeting immunotherapy that works by attaching to a protein on the surface of B-cell lymphoma cells, stimulating an immune response against the lymphoma, is also approved in the United States [as Monjuvi (tafasitamab-cxix)], Great Britain, Canada, Europe and other countries.

Professor Cheah added: "Access to novel immune therapies like MINJUVI is really important for Australian patients. Apart from CAR-T cell therapies – and these are only applicable to a certain proportion of patients with DLBCL – there have been no novel therapies for relapsed DLBCL approved in Australia. MINJUVI has a favourable side effect profile and (combined with lenalidomide) has demonstrated a high response rate in patients with relapsed disease. We now need to see it listed on the Pharmaceutical Benefits Scheme."

MINJUVI has been approved via a provisional regulatory pathway, with the TGA participating in the Modified Project Orbis initiative to accelerate availability to Australian patients. The approval was based on data from the Phase 2 L-MIND study, an open label, multi-center single arm study which evaluated its safety and efficacy in combination with lenalidomide as a treatment for patients with relapsed or refractory DLBCL who were not eligible for ASCT.[1,3]

Continued approval for this indication depends on verification and description of clinical benefit in the confirmatory Phase 3 frontMIND study which has completed enrollment.[4]

Recently, five-year follow up data were presented which showed that MINJUVI plus lenalidomide followed by MINJUVI monotherapy provided prolonged, durable responses in adult patients with relapsed or refractory DLBCL. The overall response rate (ORR) was 57.5% with a complete response (CR) observed in 41.2% of patients, and a partial response (PR) in 16.2% of patients. The median overall survival was 33.5 months and median progression-free survival (PFS) was 11.6 months.[2] The most common adverse reactions with MINJUVI are infections (73%), neutropenia (51%), asthenia (40%), anaemia (36%), diarrhoea (36%), thrombocytopenia (31%), cough (26%), oedema peripheral (24%), pyrexia (24%), decreased appetite (22%). The most common serious adverse reactions were infection (26%) including pneumonia (7%), and febrile neutropenia (6%).[1]

ST Chief Executive Officer Mr. Carlo Montagner said securing TGA approval was a key regulatory milestone for the company, noting that the therapy was synergistic with the company’s mission to provide therapies that addressed unmet needs in rare patient populations.

"We are delighted to successfully register MINJUVI for Australian patients and look forward to working with the lymphoma community to ensure it is available at the earliest opportunity," he said.

ST markets MINJUVI under an exclusive distribution arrangement with international partner Incyte (NASDAQ: INCY).

On June 27, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the grant of a new patent (number 11,684,654) entitled "Combined Preparations for the Treatment of Cancer or Infection" by the United States Patent Office (Press release, Immutep, JUN 27, 2023, View Source [SID1234632938]).

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This United States patent was filed as a second divisional application and follows the grant of the United States parent patent and first divisional patent announced in December 2020 and March 2021, respectively.

The claims of the new patent build on the protection provided by the two previously granted patents, and are directed to methods of treating cancer by administering Immutep‘s lead active immunotherapy candidate eftilagimod alpha ("efti") and a PD-1 pathway inhibitor, specifically BMS-936559, durvalumab, atezolizumab or avelumab. The expiry date of the patent is 15 November 2036 (including 312 days of patent term adjustment).

"We continue to build our patent estate around lead candidate efti, which is a unique biomolecule and shows great promise in being able to ultimately help diverse sets of cancer patients, including those with more complex needs. Here we add another key US patent which is closely aligned with our clinical development pipeline. These key patents support ongoing investment and allow us to confidently push forward across all of our business functions, including clinical, manufacturing, and business development," said Marc Voigt, CEO of Immutep.

A continuation application and a further divisional application have been filed to pursue other embodiments of the invention.

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen presenting cell (APC) activator that stimulates both innate and adaptive immunity for the treatment of cancer. Efti binds to and activates antigen-presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy.

Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On June 27, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Cancer Immunology Research1 entitled: ‘Enhancing CAR T cell therapy using Fab-Based Constitutively Heterodimeric Cytokine Receptors (Press release, Autolus, JUN 27, 2023, View Source [SID1234632937]).’

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For CAR T cells to be effective, they must engraft in the patient, expand to sufficient numbers and persist at the site of disease. Often this can involve intervals in the absence of cognate antigen, for instance during trafficking, or in the face of a hostile tumor microenvironment. T cells in a physiological immune response are supported by a network of immune cells which provide cytokine signals to stimulate proliferation and survival. CAR T cells must survive in the absence of such networks.

To address this, Righi et al describe dFabCCR, a constitutive cytokine receptor architecture. dFabCCR is a highly versatile T cell engineering component which can transmit arbitrary cytokine signals to a CAR T cell: cytokine signals normally associated with T cells such as IL2 and IL7 can be transmitted, these maintain T cells as IL2/7 exposure would do. When screening a library of different cytokine dFabCCRs, other cytokine signals such as that from IL18 or even GM-CSF had distinct functional effects on CAR T cell biology which may have therapeutic advantages in some settings.

"Achieving sufficient CAR T cell expansion and persistence can be difficult when targeting solid cancer antigens," said Dr Martin Pule, Chief Scientific Officer and Founder of Autolus. "Development of the dFabCCR architecture allows us to supply CAR T cells with versatile constitutive cytokine signals overcoming a barrier to effective CAR T cell therapies for solid cancer and is another powerful entry in our toolkit of T cell engineering components."

On June 27, 2023 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported the completion of planned patient enrollment in the Phase 1 dose escalation study evaluating the safety, tolerability, and pharmacokinetics of HPN217 in patients with relapsed/refractory multiple myeloma (Press release, Harpoon Therapeutics, JUN 27, 2023, View Source [SID1234632936]). Additional patients currently in screening will also be allowed to enroll.

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"Completing enrollment in the Phase 1 trial of HPN217 is an important step towards potentially bringing this therapy to patients with advanced disease who have progressed after prior treatments," said Luke Walker, M.D., Chief Medical Officer of Harpoon Therapeutics. "I would like to thank our patients and their caregivers, as well as our clinical partners and dedicated team of employees who have participated in this Phase 1 trial and advanced the development of HPN217."

"We are pleased to have achieved this important milestone for Harpoon, with the enrollment of the first of our two TriTAC clinical compounds having completed dose escalation as planned," said Julie Eastland, President and CEO of Harpoon Therapeutics. "The identification of the recommended dose(s) for Phase 2 and the presentation of Phase 1 data is anticipated by the end of 2023."

About the HPN217 Clinical Trial

HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody, including patients with prior exposure to BCMA therapy. Primary objectives are characterization of safety, tolerability, PK and determination of the recommended Phase 2 dose.

For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT04184050.

About HPN217

HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells. HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments.

In November 2019, Harpoon Therapeutics and AbbVie announced a licensing agreement and option to advance HPN217 and expand an existing discovery collaboration. Under the terms of the agreement, AbbVie may exercise its option to license HPN217 after completion of the Phase 1 clinical trial.

In March 2022, the FDA granted Fast Track designation to HPN217, underscoring its potential to address a serious unmet medical need for patients with relapsed, refractory multiple myeloma.