On November 22, 2023 – Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported that the INSIGHT-003 trial has been expanded to four sites across Germany including the University Clinic of Ruhr Universität Bochum and the Lung Clinic Cologne-Merheim (Press release, Immutep, NOV 22, 2023, View Source [SID1234637914]). This site expansion will support faster enrolment in this cost-efficient, investigator-initiated study evaluating eftilagimod alpha (efti) in combination with the anti-PD-1 therapy KEYTRUDA (pembrolizumab) and doublet chemotherapy for first line treatment of non-squamous non-small cell lung cancer (NSCLC).

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The strength of the early clinical data in this first-in-man triple combination study led to its increase to 50 patients. The extension opened in mid-2023 and 29 patients have been enrolled to date. With the addition of the new sites, the trial is expected to complete recruitment in 1H CY2024.

As presented at ESMO (Free ESMO Whitepaper) Congress 2023, the triple combination in INSIGHT-003 achieved a 70.6% overall response rate and 10.9-month median progression-free survival1 in patients with PD-L1 Tumor Proportion Score (TPS) of <50%, who are typically less responsive to anti-PD-1 therapy. This compares favourably to data in the same patient population, including a response rate of 40.8%, from a registrational trial of anti-PD-1 and doublet chemotherapy.2

Furthermore, the triple combination is well tolerated, and the addition of efti does not appear to increase the toxicity of KEYTRUDA and carboplatin/pemetrexed, building upon the favourable safety profile of efti that has been established across multiple clinical trials to date.

About INSIGHT-003

INSIGHT-003 is an investigator-initiated study conducted by the Frankfurt Institute of Clinical Cancer Research IKF. It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy in front line non-small cell lung cancer patients consisting of efti administered subcutaneously in conjunction with an existing approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and doublet chemotherapy (carboplatin and pemetrexed) delivered intravenously. The trial will assess the safety, tolerability, and initial efficacy of the combination.

On November 22, 2023 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it launched Phesgo combination for Subcutaneous Injection MA, IN [generic name: pertuzumab (genetical recombination), trastuzumab (genetical recombination) and vorhyaluronidase alfa (genetical recombination) ] (hereafter, Phesgo), antineoplastic agent / anti-HER2 humanized monoclonal antibody for the treatment of "HER2-positive breast cancer" and "Advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection (Press release, Chugai, NOV 22, 2023, View Source;category= [SID1234637913])." Phesgo had been approved by the Ministry of Health, Labour and Welfare (MHLW) on September 25, 2023 and was listed on the national health insurance (NHI) reimbursement price list today.

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"We are very pleased to launch Phesgo in Japan, a fixed-dose combination for subcutaneous use containing the same anti-HER2 agents of Perjeta and Herceptin, the standard therapy for HER2-positive breast cancer. Phesgo is a drug that can be administered in a shorter time than conventional intravenous injections. As lifestyles and social environments diversify, shortening infusion time is expected to improve patients’ daily lives. In addition, since it is the fixed-dose subcutaneous injection that does not require preparation, it is expected to contribute to the efficiency of medical resources. With Phesgo as a new treatment option, we will work to promote its proper use so that we can deliver unprecedented value to patients undergoing cancer treatment in various settings, their families, and healthcare providers," said Dr. Osamu Okuda, Chugai’s President and CEO.

Phesgo, this subcutaneous fixed-dose combination without preparation contains the same monoclonal antibodies as Perjeta and Herceptin, and also a vorhyaluronidase alfa (genetical recombination) combined in a single vial. It takes over eight minutes for a loading dose of Phesgo and over five minutes for the subsequent doses. By comparison, it takes 150 minutes for a sequential infusion of a loading dose of Perjeta and Herceptin using intravenous formulations (excluding follow-up observation), and 60-150* minutes for the subsequent maintenance dose infusions.1,2,3)

*Both drugs can be shortened to 30 minutes if the initial administration is well tolerated
The regulatory approval is based on the results of the global phase III FeDeriCa study including Japan and an overseas phase II PHranceSCa study. FeDeriCa study evaluated the pharmacokinetics, efficacy, and safety of Phesgo with patients with HER2-positive breast cancer. PHranceSCa study examined patient preference and satisfaction with subcutaneous administration of Phesgo in HER2-positive breast cancer.

[Approval Information]

Product name: PHESGO combination for Subcutaneous Injection MA, IN

Generic name: pertuzumab (genetical recombination), trastuzumab (genetical recombination) and vorhyaluronidase alfa (genetical recombination)

Indications:

HER2-positive breast cancer
Advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection
Dosage and administration:
< HER2-positive breast cancer >
The usual adult dosage is an initial dose of 1200 mg, 600 mg, and 30000 U of pertuzumab (genetical recombination), trastuzumab (genetical recombination), and vorhyaluronidase alfa (genetical recombination), respectively, administered subcutaneously over 8 minutes, followed by 600 mg, 600 mg, and 20000 U of the second and subsequent doses over 5 minutes every 3 weeks thereafter, in combination with other antineoplastic agents. For neoadjuvant or adjuvant therapy, the duration of treatment should be up to 12 months.
< Advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection >
The usual adult dosage is an initial dose of 1200 mg, 600 mg, and 30000 U of pertuzumab (genetical recombination), trastuzumab (genetical recombination), and vorhyaluronidase alfa (genetical recombination), respectively, administered subcutaneously over 8 minutes, followed by 600 mg, 600 mg, and 20000 U of the second and subsequent doses over 5 minutes every 3 weeks thereafter.

Date of approval: September 25, 2023

Date of NHI reimbursement price listing: November 22, 2023

Date of launch: November 22, 2023

Drug price: PHESGO combination for Subcutaneous Injection MA JPY 268,695 / bottle, IN JPY 471,565 / bottle

[Reference]
Chugai Obtains Regulatory Approval for Phesgo, the Fixed-Dose Subcutaneous Combination of Perjeta and Herceptin for HER2-Positive Breast and Colorectal Cancer (Press release issued on September 25, 2023)
View Source

About Phesgo (Pertuzumab, Trastuzumab and vorhyaluronidase alfa)
Phesgo, the fixed-dose subcutaneous combination contains the same monoclonal antibodies as Perjeta, Herceptin, and vorhyaluronidase alfa (genetical recombination) in a single vial. Hyaluronidase, an enzyme that breaks down hyaluronic acid, is considered to increase dispersion and absorption of the antibodies using Halozyme Therapeutics’ Enhanze drug delivery technology.4) The monoclonal antibodies in Phesgo are identical to those in Perjeta and Herceptin. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but in different locations.5,6) The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.5,6)

About FeDeriCa study7)
FeDeriCa study is an international, multi-center, two-arm, randomized, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of subcutaneous injection of the fixed-dose combination of Perjeta and Herceptin in combination with chemotherapy, compared with standard intravenous infusions of Perjeta and Herceptin in combination with chemotherapy in 500 people with HER2-positive early breast cancer who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and pathological complete response (pCR) in the breast and axilla.

About PHranceSCa study8)
PHranceSCa study is an overseas phase II randomized clinical study to evaluate patient preference and satisfaction for the fixed-dose combination of Perjeta and Herceptin for subcutaneous injection in 160 patients with HER2-positive early breast cancer. The primary endpoint is patient’s preference for this drug based on responses to the Patient Preference Questionnaire (PPQ). Secondary endpoints include patient satisfaction with this drug and Perjeta and Herceptin intravenous formulations as measured by the Therapy Administration Satisfaction Questionnaire (TASQ), and patient’s selection of this drug during continued treatment.

Trademarks used or mentioned in this release are protected by law.

On November 22, 2023 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that a patient who participated in the Phase II Liver Cancer Study and was treated with namodenoson has a complete response and overall survival of 6.9 years (82.8 months) (Press release, Can-Fite BioPharma, NOV 22, 2023, View Source [SID1234637898]).

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Liver Cancer designated as hepatocellular carcinoma (HCC), is a major global health problem due to its incidence, associated mortality, and lack of effective treatment modalities, particularly for patients with advanced hepatic dysfunction known as disease stage Child Pugh B.

A patient with advanced HCC that was enrolled in the former Can-Fite Phase II study continues to receive treatment with namodenoson and has now an overall survival of 6.9 years with the disappearance of ascites, normal liver function, and good quality of life and defined as a complete response.

Can-Fite has received agreement from both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) on a pivotal Phase III clinical study which is now enrolling patients in Israel, Europe and the US. Namodenoson has Orphan Drug status with both the FDA and EMA, as well as Fast Track Status with the FDA for the treatment of HCC. A compassionate use program has been ongoing in Israel and Romania.

The double blind, placebo-controlled trial will enroll 450 patients diagnosed with HCC and underlying Child Pugh B7 (CPB7) through clinical sites worldwide. Patients will be randomized to oral treatment with either 25 mg Namodenoson or matching placebo given twice daily. The primary efficacy endpoint of the trial is overall survival. Other oncology trial efficacy outcomes, such as tumor radiographic response rates and median progression-free survival, as well as standard safety parameters, will be assessed.

An interim analysis will be conducted by an Independent Data Monitoring Committee (IDMC) after 50% of enrolled patients are treated. Namodenoson will be evaluated as a 2nd or 3rd line treatment for CPB7 patients in whom other approved therapies have not been or are no longer effective.

"We are currently enrolling patients for the pivotal Phase III clinical study and hope that if the interim analysis data will be positive, we will be able to get a conditional approval, and that patients who suffer from this devastating disease will enjoy our drug" stated Can-Fite CEO Motti Farbstein.

According to the American Cancer Society, liver cancer accounts for more than 700,000 deaths globally each year. HCC is commonly aggressive with poor survival rates. As new drugs that effectively and safely treat HCC are developed and approved, the market for HCC treatments is estimated by Delveinsight to reach $3.8 billion by 2027 for the G8 countries.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On November 21, 2023 Oncoteq AG, a clinical stage biotech company specializing in innovative cancer treatments, expands its pipeline with the in-licensing of the small molecule TEQ103 (formerly SERA2) from US biotech incubator, Systems Oncology (Press release, Cureteq, NOV 21, 2023, View Source [SID1234651624]). The agreement represents Oncoteq’s second in-licensing of a potential first-in-class or best-in-class cancer treatment following its transaction with Merck KGaA in 2022. The company will continue to seek opportunities with which to expand its growing oncology-focused pipeline.

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TEQ103 is a first-in-class selective estrogen receptor activator (SERA) that potentially offers a paradigm-shifting treatment approach for patients with breast cancer. TEQ103 utilises a novel mechanism directed towards estrogen receptor alpha (ER), a proven target for the treatment of patients with breast cancer. Through high-affinity binding to ER TEQ103 exerts lethal effects only in cells that have an activated stress response, so-called anticipatory unfolded protein response (aUPR), a feature absent in healthy cells. This pushes a normally protective cellular stress-response pathway into overdrive and rapidly and selectively kills ER-expressing cancer cells. Current ER- targeting ("endocrine") breast cancer treatments act to slow tumor growth by modulating or degrading ER or by lowering estrogen levels and lack selectivity for cancer cells.

Breast cancer is among the most frequent of cancers and annually more than an estimated 350,000 patients lose their lives to the disease. Given that around 80% of all breast cancers express ER, TEQ103 may represent a paradigm shift in treatment for a large group of breast cancer patients.

"We are thrilled by the opportunity to bring forward a potentially highly effective treatment for breast cancer, a disease still characterized by significant unmet medical needs despite recent advances in treatment. We are excited to progress this molecule as fast as possible to clinical testing, knowing that it could be a potential game changer for breast cancer patients in great need", says Mads Dalsgaard, Chief Executive Officer of Oncoteq.

Spyro Mousses, Chief Executive Officer of Systems Oncology, comments: "We are really impressed with the team at Oncoteq and their vision of how to take this molecule forward to a new groundbreaking breast cancer treatment. It is pleasure to hand over the future development to Oncoteq and have them build upon what we started, first and foremost to benefit patients"

TEQ103 is currently in pre-clinical development and Oncoteq will complete the non-clinical data package before advancing the molecule into clinical development in 2025. Oncoteq will firstly prioritize development of TEQ103 as treatment of breast cancer and could later expand to other indications, as the compound has potential as a treatment for several other cancers. Currently, the global market for breast cancer treatments has a value of approximately USD 25-30 billion annually, thus TEQ103 has significant potential not only for patients but also commercially.

Through the deal, Oncoteq obtains a world-wide exclusive license to develop and commercialize TEQ103 in exchange for upfront payment, milestones and royalties.

On November 21, 2023 BroadenBio reported that the company successfully completed the administration of the first patient in Phase I clinical trials of the independently developed, small molecule HPK1 inhibitor BB3008 at the Cancer Hospital Chinese Academy of Medical Sciences (Press release, BroadenBio, NOV 21, 2023, View Source [SID1234640207]). This clinical trial is led by Professor Jing Huang from the Cancer Hospital Chinese Academy of Medical Sciences, which aims to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of oral BB3008 tablets in patients with advanced solid tumors. Currently, no drug with the same target has been approved for marketing in the world, and all candidates are in the early clinical research stage.

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BB3008 is a highly potent and selective small molecule inhibitor of HPK1 that has been approved by China NMPA and the US FDA. It is currently undergoing phase I clinical trials in China for patients with advanced solid tumors regardless of cancer type. HPK1 is an intracellular immune checkpoint mainly expressed in immune cells (T cells, B cells, dendritic cells, macrophages, and etc.). It is a key negative feedback regulator of the T cell receptor (TCR) signaling pathway and inhibits the immune function of T cells. As a highly selective HPK1 inhibitor, BB3008 activates the anti-tumor function of T cells by blocking the HPK1-mediated negative feedback mechanism of TCR signaling, and breaks through the limitation of insufficient response rates of current immune checkpoint inhibitors. In preclinical studies, BB3008 showed significant tumor-growth inhibition efficacy in various syngeneic mouse tumor models, and synergic anti-tumor effect in combination with PD-1 antibody. BB3008 has good safety profiles, and no immune-related adverse effect has been observed in preclinical animal experiments.

"The successful administration of BB3308 for the first patient means that BB3008, as a clinical drug candidate, has entered the global competition for clinical development on the innovative target HPK1. I would like to express my sincere thanks to the team of Professor Jing Huang from the Cancer Hospital Chinese Academy of Medical Sciences for their strong support, and I am also grateful to the company’s team for their devotion," said Xingmin Zhang, M.D., Ph.D., founder and Chief Executive Officer of BroadenBio. "We look forward to efficiently promoting the clinical research of BB3008 continuously with everyone’s joint efforts and benefiting cancer patients as soon as possible."