On October 31, 2022 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported that its Phase 1 MAST (metastatic advanced solid tumours) study evaluating the safety of novel cancer-killing virus CF33-hNIS (VAXINIA) has advanced with the first patient dosed within intratumoral (IT) cohort 2 of the trial (Press release, Imugene, OCT 31, 2022, View Source [SID1234622596]).

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This follows the announcement in September that the first patient had been dosed as part of the intravenous (IV) cohort 1 of the study.

A multicenter Phase 1 trial, the VAXINIA Phase 1 MAST study has to date delivered a low dose to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. The City of Hope-developed oncolytic virus has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models¹.

The clinical trial is titled "A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33-hNIS), Administered Intratumorally or Intravenously as a Monotherapy or in Combination with Pembrolizumab in Adult Patients with Metastatic or Advanced Solid Tumours (MAST)." The trial is anticipated to run for approximately 24 months and is funded from existing budgets and resources.

Imugene MD & CEO, Ms Leslie Chong said: "The VAXINIA trial continues to progress on schedule and we’re very excited to see the results it can deliver for these patients dealing with significant tumour growth."

On October 28, 2022 Alphamab Oncology (stock code: 9966.HK) reported the IND application to conduct a Phase Ia/Ib Clinical Trial of Anti-HER2 bispecific ADC was approved by the Center for Drug Evaluation (CDE) of NMPA (Press release, Alphamab, OCT 30, 2022, View Source [SID1234632919]). The study will evaluate the safety and tolerability of JSKN003 in Chinese patients with advanced malignant solid tumors, and to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D).

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According to the latest report released by the National Cancer Center in 2022, the incidence of cancer in China continues to rise, with more than 11,100 people are diagnosed with tumors every day, among which lung cancer, colorectal cancer, gastric cancer, liver cancer and female breast cancer account for 57.4% of the total new cases. Human epidermal growth factor receptor-2 (HER2) is an effective target for the treatment of a variety of advanced malignant solid tumors, and antibody-drug conjugates (ADCs) have been shown to significantly improve the clinical efficacy. Therefore, exploring novel HER2-targeting antibody-drug conjugates could provide new treatment options for more cancer patients.

JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (ADC), which is developed inhouse with proprietary Glycan-specific conjugation platform. Through enzyme catalysis and click chemistry, the payloads are site-specifically linked to glycan on Fc. The glycan structure is precisely controlled via process engineering which renders consistant DAR with more favorable stability. Compared other ADC drugs, JSKN003 induce faster and more intense endocytosis, which leads to stronger bystander effect in HER2-expressing tumors. Meanwhile the better serum stability ensures much wider therapeutic window. For example, JSKN003 shows better safety profile in preclinical study and comparable tumor killing activity with Enhertu (DS-8201) in both high and low HER2 expression (CDX+PDX model). A phase I clinical dose escalation study in underway in Australia for JSKN003 and the first patient was dosed in September 2022.

About JSKN003
JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (ADC), which is developed inhouse with proprietary Glycan-specific conjugation platform. JSKN003 targets HER2 and triggers a signal in the tumor cell, which then internalizes the antibody together with the payload. After endocytosis, the cytotoxic drug is released and kills the cancer cells. Compared other ADC drugs, JSKN003 induce faster and more intense endocytosis, which leads to stronger bystander effect in HER2-expressing tumors. Meanwhile the better serum stability ensures much wider therapeutic window. A Phase I, multicenter, open-label, dose-escalation, first-in-human trial in Australia is ongoing to assess safety and tolerability in patients with advanced or metastatic solid malignancies and to determine the maximum tolerated dose /RP2D. The phase I clinical study application of JSKN003 in China for treatment of advanced solid tumors was approved by NMPA.

On October 30, 2022 GenesisCare, a leading provider of integrated cancer care globally, and Prelude Corporation (PreludeDx(TM)), a leader in molecular diagnostics and precision medicine, reported interim results from the AUSPREDICT registry (Press release, GenesisCare, OCT 30, 2022, https://www.prnewswire.com/news-releases/genesiscare-and-preludedxtm-present-compelling-australian-first-dcisionrt-study-interim-analysis-during-breast-cancer-awareness-month-45-change-in-treatment-recommendations-when-using-dcisionrt-301662105.html [SID1234622599]). Data presented at the Australasian International Breast Congress demonstrates a significant (45%) change in radiation therapy treatment recommendations1 when using the DCISionRT test, optimising management to prevent over and under treatment of Australian women with Ductal Carcinoma In Situ (DCIS).

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DCIS is a pre-invasive disease of the breast that may lead to invasive breast cancer if untreated.(2) After breast conserving surgery (BCS) for DCIS, radiation therapy is often used to minimise the risk of recurrence. DCISionRT(R)is a novel molecular test that assesses the 10-year risk of recurrence after BCS and if there would be a benefit to treating with radiation therapy. GenesisCare and PreludeDx formed a strategic partnership in 2021 to bring DCISionRT to Australia for the first time and establish the AUS-PREDICT registry to collect real-world data to further the development of precision medicine and decision tools globally.

The presentation, entitled Interim Analysis of the PREDICT Registry Australia: Changes in Treatment Recommendation for a Biologic Signature Predictive of Radiation Therapy (RT) Benefit in Patients with DCIS, studied 232 patients from Australia who had received the DCISionRT test following breastconserving surgery. Radiation therapy recommendation decreased by 70% in patients with a low risk DCISionRT score and increased 29% in patients with elevated risk scores.(1)

Leading Specialist Breast Surgeon and Director of Breast Cancer Services for Royal Melbourne and Royal Women’s Hospital, Melbourne, Professor Bruce Mann, said: "Historically, we have relied on clinical pathology, such as tumour grade and size, to determine treatment plans for patients with DCIS. This data demonstrates the integration of DCISionRT into clinical decision making has a substantial impact on RT recommendations and has the ability to prevent over and under treatment of DCIS patients."

Principal Investigator and GenesisCare Radiation Oncologist, Dr Yvonne Zissiadis, said the interim results "demonstrate the critical role of DCISionRT in the clinical treatment pathway for DCIS patients, ensuring women receive the right treatment at the right time. "Our study highlights that DCISionRT is a promising predictive tool, arming clinicians and patients with the information to make informed decisions about treatment options based on a patient’s individual biological risk profile."

"GenesisCare, in partnership with PreludeDx, is thrilled to present the interim findings from our Australian-first study," continued Dr Zissiadis.

"The first interim analysis of AUS-PREDICT is highly consistent with the US-PREDICT registry3 that has completed enrollment of 2,500 patients," said Troy Bremer, PhD, Chief Scientific Officer of PreludeDx. "In the registry studies in both countries, DCISionRT was the most impactful single factor for changing treatment recommendations regarding radiation therapy following breast conserving surgery," continued Dr. Bremer.

"We are delighted to bring precision medicine to Australian women diagnosed with DCIS and further enrollment in the AUS-PREDICT registry. We look forward to the continued expansion of our global data network and clinical evidence for DCISionRT," said Dan Forche, CEO of PreludeDx.

On October 30, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that the first patient was dosed in Australia for its proprietary anti-Claudin18.2 monoclonal antibody-drug conjugate(ADC) (R&D code: IBI343) in Phase I clinical trial for the treatment of patients with advanced solid tumors (Press release, Innovent Biologics, OCT 30, 2022, View Source [SID1234622598]). It is the first ADC candidate drug to enter clinical phase in Innovent’s pipeline.

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The study (NCT05458219) is an open-label, multi-center Phase I study evaluating the safety, tolerability, and preliminary efficacy of IBI343 in subjects with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D).

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal ADC. After IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization occurred and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect". In both Claudin 18.2 high and low expression mice tumor bearing models, IBI343 exhibited potent tumor growth inhibition efficacy, and it also demonstrated tolerable safety profile in preclinical in vivo models.

Dr. Andrea Tazbirkova, Pindara Private Hospital Located in Queensland, Australia, stated： "Claudin 18.2 has emerged as an ideal anti-tumor target and has been clinically validated by different modalities including mono-antibodies and CAR-T therapy with manageable toxicity. Nonetheless, the efficacy is selective and limited within cancer patients with CLDN18.2-high expression, leaving unmet need for patients with CLDN18.2 low-expressing tumors. IBI343 is Claudin 18.2 targeting ADC with bystander effect and has demonstrated promising anti-tumor effect in Claudin 18.2-high and low in-vivo models with tolerable safety profile. We look forward to the positive results in the safety/tolerability and efficacy of IBI343 in the clinic."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: " At present, target treatment options are limited for gastric and pancreatic cancer where imply huge unmet clinical needs. High expression of Claudin 18.2 in aforesaid tumors suggests its high potential and Innovent has been actively rolling out a cluster of Claudin 18.2 drug candidates across different modalities to seek for differentiated therapeutic values while guarantee druggability. We are pleased that the first patient dose of IBI343 has been completed in Australia. In parallel, the IND for IBI343 has been filed in China last month. We are looking forward to the positive results of IBI343 in patients with advanced solid tumors. IBI343 is our first ADC molecule to initiate clinical study in both Australia and China, adding a valuable clinical asset in our R&D pipeline that represents Innovent’s global innovation strategy. The company will also accelerate the development of more innovative molecules with high global potential, taking advantage of cross-regional R & D and clinical resources, adhering to the long-term development strategy of ‘driven by innovation, developed through globalization’with an aim to benefit cancer patients worldwide."

About Claudin 18.2

Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectal cancer. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors.

Globally, there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products. However, currently no drug targeting Claudin18.2 has been approved.

About IBI343

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization will occurr and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect". Currently, Phase I study of IBI343 has been conducted in Australia (NCT05458219) to assess the safety, tolerability, and preliminary efficacy of IBI343 in subjects with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

On October 30, 2022 Akeso, Biopharma (9926. HK) ("Akeso") reported the Phase Ib clinical results of Ivonescimab (PD-1/VEGF bi-specific, AK112) in combination with etoposide and carboplatin in first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC), in an oral presentation at the IASLC 2022 Asia Conference on Lung Cancer (Press release, Akeso Biopharma, OCT 30, 2022, View Source [SID1234622597]).

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Preliminary data of AK112 combination with etoposide and carboplatin showed a favorable safety profile and promising anti-tumor efficacy as first-line treatment in patients with ES-SCLC and may be a promising treatment option. Compared to the data from marketed PD-L1 inhibitors in combination with chemotherapy, AK112 in combination with chemotherapy demonstrated superior antitumor efficacy and survival benefit.

As of June 1, 2022, all patients had received at least one dose of AK112. The median follow-up time was 7.2 months.

Median progression-free survival (PFS) was 6.9 months, with a 6-month PFS rate of 52.1%,
Objective remission rate (ORR) was 87.5%, and disease control rate (DCR) was 96.9%.
Overall survival (OS) data are not mature.
No new safety signal was observed.
Lung cancer is one of the most common cancers globally and in China, with up to two-thirds of SCLC patients having ES-SCLC at first diagnosis, and etoposide + platinum has been the standard of care for first-line treatment of ES-SCLC for more than 30 years. Two PD-L1 inhibitors have been approved in combination with chemotherapy to treat ES-SCLC, but the survival benefit for patients remains very limited.

Two Phase III trials of Ivonescimab for major lung cancer indications are currently being conducted efficiently, including Ivonescimab plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy, and Ivonescimab monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression.

Related Studies:

Atelelizumab (PD-L1) in combination with carboplatin and etoposide, was approved for the first-line treatment of ES-SCLC (IMpower133) which had a median PFS of 5.2 months, a median OS of 12.3 months, and an ORR of 60.2%. [1] [2]

Dulvalizumab (PD-L1) in combination with etoposide and either carboplatin or cisplatin, was approved for the first-line treatment of ES-SCLC (CASPIAN) which had a median PFS of 5.1 months, an ORR of 68%, and a median OS of 13 months[3]