On September 3, 2024 AVEO Oncology, an LG Chem company ("AVEO"), reported their late-breaking abstract detailing their Phase 3 TiNivo-2 trial has been selected as a Proffered Paper oral presentation at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona, Spain this September 13-17th (Press release, AVEO, SEP 3, 2024, View Source [SID1234646325]).

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The oral presentation will announce the results from the TiNivo-2 clinical trial, which was designed to evaluate the benefit of adding nivolumab, a PD-1 checkpoint inhibitor, to low dose (0.89mg) FOTIVDA (tivozanib), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) versus standard dose (1.34mg) FOTIVDA in the second-line following immune checkpoint inhibitor (ICI) combinations or the third-line setting following prior ICI treatment. Details of the presentation are as follows:

Title:

Tivozanib Plus Nivolumab vs Tivozanib Monotherapy in Patients With
Metastatic Renal Cell Carcinoma Following an Immune Checkpoint
Inhibitor: Results of the Phase 3 TiNivo-2 Study

Speaker:

Toni Choueiri, MD, Director of the Lank Center for Genitourinary (GU)
Oncology at Dana-Farber Cancer Institute, Boston, MA, United States of America

Presentation #:

LBA73

Category:

Proffered Paper session 1: GU tumors, non-prostate

Date & Time:

Friday, September 13, 2024; 2:00 – 2:10 pm CET

TiNivo-2 Clinical Trial Details
Phase 3 clinical trial designed to evaluate the safety and efficacy of tivozanib in combination with nivolumab, as compared to tivozanib as a monotherapy, in RCC patients whose tumors progressed following prior ICI therapy.

About FOTIVDA (tivozanib)
FOTIVDA (tivozanib) is an oral, next-generation VEGFR 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, based on data from the TIVO-3 trial comparing FOTIVDA to sorafenib. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner Recordati UK Ltd. for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTION

Hypertension was reported in 45% of patients (22% ≥ Grade 3). Hypertensive crises were reported in 0.8% of patients. Do not initiate FOTIVDA in patients with uncontrolled hypertension. Monitor for hypertension and treat as needed. Reduce the FOTIVDA dose for persistent hypertension not controlled by anti-hypertensive medications. Discontinue FOTIVDA for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Cardiac failures were reported in 1.6% of patients (1% ≥ Grade 3); 0.6% of events were fatal. Monitor for signs or symptoms of cardiac failure during treatment with FOTIVDA. Manage with dose interruption, dose reduction, or discontinuation.

Cardiac ischemia were reported in 3.2% of patients; 0.4% of events were fatal. Arterial thromboembolic events were reported in 2.0% of patients, including death due to ischemic stroke (0.1%). Closely monitor patients at risk for, or who have a history of these events. Discontinue FOTIVDA in patients who develop severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thrombotic Events (VTE) were reported in 2.4% of patients, including 0.3% fatal events. Closely monitor patients who are at increased risk for these events. Discontinue in patients who develop serious VTEs.

Hemorrhagic Events were reported in 11% of patients; 0.2% of events were fatal. Use FOTIVDA with caution in patients who are at risk for or who have a history of bleeding.

Proteinuria was reported in 8% of patients (2% = Grade 3). Monitor during treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or interrupt treatment. Discontinue in patients who develop nephrotic syndrome.

Gastrointestinal (GI) Perforation including fatal cases, has been reported in patients receiving FOTIVDA. Monitor for symptoms of GI perforation or fistula formation periodically throughout treatment with FOTIVDA. Permanently discontinue FOTIVDA in patients who develop severe or life-threatening GI perforation.

Thyroid Dysfunction events were reported in 11% of patients (0.3% ≥ Grade 3). Monitor thyroid function before and during treatment with FOTIVDA.

Wound Healing Complications: Withhold FOTIVDA for at least 24 days prior to elective surgery and do not administer for at least 2 weeks after major surgery and until adequate wound healing is observed.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) can occur with FOTIVDA. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue if signs or symptoms of RPLS occur.

Embryo-fetal Toxicity: FOTIVDA can cause fetal harm. Advise patients of the potential risk to a fetus, to avoid becoming pregnant and to use contraception during treatment and for one month after the last dose of FOTIVDA. Advise males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of FOTIVDA.

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

ADVERSE REACTIONS

Common adverse reactions include fatigue/asthenia, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis.

Serious adverse reactions include bleeding (3.5%), venous thromboembolism (3.5%), arterial thromboembolism (2.9%), acute kidney injury (2.3%), and hepatobiliary disorders (2.3%).

DRUG INTERACTIONS

Avoid coadministration with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Advise women not to breastfeed during treatment and for at least 1 month after the last dose.

The recommended dosage for patients with end-stage renal disease has not been established.

Reduce the FOTIVDA dose for patients with moderate hepatic impairment. The recommended dosage in patients with severe hepatic impairment has not been established.

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 full Prescribing Information for FOTIVDA (tivozanib).

On September 3, 2024 Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, reported that Lunit SCOPE IO has demonstrated significant potential in predicting immunotherapy response for patients with advanced biliary tract cancer (BTC), via AI-powered analysis of immune phenotype and tumor-infiltrating lymphocytes (TILs) (Press release, Lunit, SEP 3, 2024, View Source;new-publication-in-ccr-302236317.html [SID1234646324]). The groundbreaking study, conducted in collaboration with researchers from Asan Medical Center and Severance Hospital in Seoul, Korea, was recently published in Clinical Cancer Research (CCR), an AACR (Free AACR Whitepaper) journal.

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BTC is known for its poor prognosis, with limited treatment options available. While recent studies have shown promise in combining immunotherapy, such as anti-PD-1 inhibitors with standard chemotherapy, there has been a lack of effective predictive tools to guide treatment decisions.

The study analyzed pre-treatment pathology samples (H&E slides) from 339 patients with advanced BTC who received anti-PD-1 monotherapy as second-line or later treatment. Using Lunit SCOPE IO, researchers performed a detailed analysis of the tumor microenvironment, classifying patients’ immune phenotypes into three categories: inflamed (high intratumoral TIL), immune-excluded (low intratumoral TIL and high stromal TIL), and immune desert (low TIL overall). Immune phenotypes are an emerging pan-cancer biomarker with support from leaders of the immuno-oncology community.[1]

Key findings include:

Patients classified as having an "inflamed" immune phenotype showed significantly better treatment outcomes compared to those with non-inflamed phenotypes, as consistent with previously published studies.[2]
The inflamed group demonstrated both longer overall survival (12.6 vs. 5.1 months) and progression-free survival (4.5 vs. 1.9 months), as well as higher overall response rates (27.5% vs. 7.7%).
Lunit SCOPE IO provided objective and efficient assessment of the tumor microenvironment, overcoming limitations of manual evaluation demonstrating high feasibility for AI-powered analysis of immune phenotype and TIL.
Notably, this study suggests immune phenotyping can serve as a predictive biomarker for possible response to immunotherapy in BTC, addressing a long-standing gap in personalized treatment approaches for this class of cancers with a high unmet need.

"Lunit SCOPE IO represents a significant advancement in the precision medicine landscape for cancer treatment," said Brandon Suh, CEO at Lunit. "By providing a deeper understanding of the tumor microenvironment, particularly immune phenotyping, our AI technology empowers clinicians to make informed treatment decisions, identifying patients most likely to benefit from immunotherapy and opening new avenues for personalized treatment strategies in challenging cancer types."

On September 3, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) ("Jazz Pharmaceuticals") reported that Jazz Investments I Limited, its wholly-owned subsidiary (the "Issuer"), intends to offer, subject to market conditions and other factors, $850 million aggregate principal amount of exchangeable senior notes due 2030 (the "notes") in a private offering (the "offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Jazz Pharmaceuticals, SEP 3, 2024, View Source [SID1234646323]). The Issuer also expects to grant the initial purchasers of the notes an option, exercisable within a period of 13 days from and including the date the notes are first issued, to purchase up to an additional $150 million aggregate principal amount of notes.

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The notes will be exchangeable under certain conditions. The Issuer will settle exchanges by paying cash up to the aggregate principal amount of the notes to be exchanged. The remainder, if any, of the Issuer’s exchange obligation in excess of the aggregate principal amount of the notes, will be settled in cash, ordinary shares of Jazz Pharmaceuticals ("ordinary shares") or a combination of cash and ordinary shares, at the Issuer’s election. The interest rate, initial exchange rate and other terms of the notes will be determined at the time of pricing of the offering.

The notes will be general unsecured obligations of the Issuer and will accrue interest payable semiannually in arrears. The Issuer’s obligations under the notes will be fully and unconditionally guaranteed on a senior unsecured basis by Jazz Pharmaceuticals; will rank pari passu in right of payment with the Issuer’s existing 2.000% exchangeable senior notes due 2026; will be effectively subordinated to the Issuer’s guarantees of the indebtedness under Jazz Pharmaceuticals’ credit agreement (the "credit agreement") and Jazz Pharmaceuticals’ 4.375% senior secured notes due 2029 (the "senior secured notes") to the extent of the value of the assets securing such guarantees; and will be structurally subordinated to the indebtedness and guarantees under the credit agreement and the senior secured notes of Jazz Pharmaceuticals’ other subsidiaries that are borrowers or have provided guarantees of such indebtedness.

Jazz Pharmaceuticals, together with its consolidated subsidiaries ("Jazz"), expects to use a portion of the net proceeds to prepay up to approximately $350 million of the term loans outstanding under the credit agreement and the remainder for general corporate purposes. If the initial purchasers exercise their option to purchase additional notes, Jazz expects to use the net proceeds from the sale of the additional notes for further prepayments of the term loans.

Jazz Pharmaceuticals also expects to repurchase up to $150 million of its ordinary shares from purchasers of the notes in privately negotiated transactions with or through one of the initial purchasers or its affiliate concurrently with the pricing of the offering (the "concurrent ordinary share repurchases"). Jazz Pharmaceuticals expects the purchase price per ordinary share repurchased in such concurrent ordinary share repurchases to equal the closing price per ordinary share on the date of the offering. To the extent Jazz Pharmaceuticals effects any such concurrent ordinary share repurchases, it will pay for such repurchases with existing cash on hand and such repurchases will be effected as part of Jazz Pharmaceuticals’ share repurchase program announced in July 2024. Accordingly, any such concurrent ordinary share repurchases will reduce the remaining amount authorized under the share repurchase program. No assurance can be given as to how much, if any, of Jazz Pharmaceuticals’ ordinary shares will be repurchased or the terms on which they will be repurchased. The concurrent ordinary share repurchases could increase, or reduce the size of any decrease in, the market price of the ordinary shares, including concurrently with the pricing of the notes, resulting in a higher effective exchange price for the notes. This press release is not an offer to repurchase the ordinary shares, and the offering of the notes is not contingent upon the repurchase of any ordinary shares.

None of the notes, the guarantee or the ordinary shares issuable upon exchange of the notes, if any, have been registered under the Securities Act or the securities laws of any other jurisdiction, and, unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of the securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state or jurisdiction.

On September 3, 2024 Biostar Pharma, Inc., the US subsidiary of Beijing Biostar Pharmaceuticals Co., Ltd. which is a synthetic biology driven biopharma company focusing on the discovery, development and commercialization of innovative oncology drugs, reported that subject recruitment of a US Phase 1 clinical study of Utidelone Capsule (UTD2), a company’s key pipeline product, for advanced solid tumors (NCT05681000) has been completed (Press release, Biostar, SEP 3, 2024, View Source [SID1234646322]).

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This study is an open-label, dose-escalation Phase 1 clinical study, and conducted in several institutions across the US including Sarah Cannon Research Institute (Florida Cancer Specialists & Research Institute), University of Southern California, and the Washington University in St. Louis. The primary objective of this study is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT); the secondary objective is to evaluate the efficacy and pharmacokinetic profile of UTD2 monotherapy in patients with advanced solid tumors.

Five dose cohorts were explored in this study. After confirming the DLT (diarrhea) in the highest dose cohort, 75mg/m2/day x 5 days was determined as MTD. A total of 18 patients with more than 10 different types of advanced solid tumors were enrolled. The median age was 63 years old, and 2/3 of the patients had received ≥ 3 lines of prior treatments. As of now, efficacy evaluations were completed in 12 patients, and 1 complete response (CR, ovarian cancer), 1 partial response (PR, ovarian cancer), and 8 stable disease (SD, prostate cancer, testicular cancer, non-small cell lung cancer, pancreatic cancer, appendix adenocarcinoma, soft tissue sarcoma, etc.) were obtained with a clinical benefit rate of 83%. The results further demonstrated the broad-spectrum anti-tumor property of Utidelone. As for treatment duration, more than half of these patients received ≥3 cycles of treatments, and the maximum duration of response reached 36 weeks. In terms of safety, most treatment-related adverse events (TRAEs) were grade 1-2, and the most frequently seen TRAEs (incidence ≥ 20%, including all grades) were diarrhea (55.6%), fatigue (33.3%), and neutropenia (22.2%), all of which were manageable. The preliminary results of this study were also presented at the 2024 ASCO (Free ASCO Whitepaper) meeting.

Dr. Li Tang, Chairman of Biostar Pharma commented: "This is the first study of UTD2 that has completed enrollment globally. We successfully achieved the primary objectives and observed encouraging efficacy and safety profiles. We are very grateful for the joint engagement and dedication of our US clinical institutions and investigators. We are confident that this blockbuster product will substantially change the administration regimen of microtubule inhibitors. We will advance the following pipelines for UTD2 at full speed and hopefully bring it to the market to benefit global cancer patients as soon as possible".

Biostar is actively carrying out clinical studies of UTD2 in China and abroad. A pivotal study in China for advanced breast cancer led by Professor Xu Binghe, Cancer Hospital of Chinese Academy of Medical Sciences, is in recruitment. The preliminary findings of this study were also presented at the ASCO (Free ASCO Whitepaper) meeting in 2024; the China Phase 2 study for advanced solid tumors including ovarian cancer and cholangiocarcinoma, etc. is in initiation. In addition, US FDA has granted an Orphan Drug Designation (ODD) to UTD2 for the treatment of advanced gastric cancer, and Biostar is preparing for IND filing of a Phase 2/3 multi-reginal clinical study (MRCT) led by Professor Ruihua Xu of Sun Yat-sen University Cancer Center in both China and US simultaneously.

Utidelone is a new-generation genetically engineered microtubule inhibitor. Utidelone Injection (UTD1) has been launched in China in 2021 for the treatment of metastatic breast cancer (MBC) progressed after at least one anthracycline- or taxane-containing chemotherapy regimen. The phase 3 study data showed that UTD1 is the only one to achieve both PFS and OS benefits for heavily pretreated MBC patients, and the results were twice orally presented at ASCO (Free ASCO Whitepaper) annual meetings. Utidelone has similar mechanism of action with that of taxanes while demonstrating multiple advantages, including better anti-tumor activity, broader anti-tumor spectrum, better safety profile with very low hematologic toxicity, effective against multidrug-resistant tumors with less prone to develop drug resistance, capability of crossing the blood-brain barrier so as to prevent and treat brain tumor, and high oral bioavailability. Multiple indication expansion clinical studies for UTD1 are also in progress in China and US, including but not limited to MRCT Phase 3 study for non-small-cell lung cancer (NSCLC), Phase 2 pivotal study for breast cancer brain metastasis in US and NSCLC brain metastasis in China, and Phase 3 study for breast cancer neoadjuvant in China.

Compared to taxanes, which are difficult for oral formulation development, Utidelone is not susceptible to P-glycoprotein thus cannot be pumped out of the cancer cell by P-glycoprotein and has the advantage for higher oral bioavailability. By utilizing its synthetic biology technology platform, Biostar developed Utidelone Capsule, and its efficacy and safety have been confirmed in both US and China’s studies. Utidelone Capsule will significantly improve the convenience of administration, compliance of patients, decrease in treatment cost and ease of combination therapy with other oral anti-cancer drugs, meaning more suitable for adjuvant and maintenance therapy.

On September 3, 2024 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, reported dosing of 5 new patients in the ACHIEVE Phase 2b trial ongoing in the UK (Press release, TC Biopharm, SEP 3, 2024, View Source [SID1234646321]).

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Currently, the trial has successfully dosed 6 patients with their first of 4 possible doses at the higher dose level. Each 5mL dose contains up to 230 million gamma delta T cells, and a patient is expected to receive up to an approximate 1 billion gamma delta T cells over four doses. Five patients have received their second dose, with 2 of these patients having also received their third dose. This correlates with TCBP’s step-wise approach to process improvements, as implemented in Q4 2023, and further steps taken to amend the trial protocol in the first quarter of 2024. New patients will continue to be identified, screened, and enrolled into the study.

"TCBP is excited to announce our rapid progression in the ACHIEVE Phase 2b trial with very strong enrolment in the second part of the trial using the higher dose," stated, Bryan Kobel, CEO of TC BioPharm. "TCB008 is potentially a game-changing monotherapy for blood cancers, and the strong recruitment and patient retention rates are testament to clinician/physician interest in TCB008 as a monotherapy in leukemia. We’re proud of the milestones accomplished to date, having rapidly dosed 6 patients with an additional 10 patients lined up. It is encouraging to see re-dosing of several patients, which we believe reflects positively on the steps the organization took in 2023 and early 2024. TCBP remains poised to execute on our clinical trial plans in 2024 and into 2025, including ACHIEVE and ACHIEVE2, as well as our expanded manufacturing capabilities to enhance our operational capabilities and our economic efficiencies."

The ACHIEVE UK clinical trial is an open-label, phase II study designed to evaluate the efficacy and effectiveness of TCB008 in patients with AML or MDS/AML, with either refractory or relapsed disease.