On November 7, 2023 AdvanCell, a radiopharmaceutical company developing a pipeline of Targeted Alpha Therapies for cancer patients, reported the first patient was treated with 212Pb-ADVC001, a Targeted Alpha Therapy in development for the treatment of PSMA-positive metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, Advancell, NOV 7, 2023, View Source [SID1234637197]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We believe that 212Pb is the ideal radioisotope to realise the full therapeutic power of Targeted Alpha Therapy. This promise is strongly supported by preclinical results for 212Pb-ADVC001, which demonstrate the potential for best-in-class safety and efficacy."

Post this
"The first patient dosed with an AdvanCell therapeutic candidate represents a major milestone for the Company, our scientists, clinical trial sites, and our patients," said Andrew Adamovich, CEO of AdvanCell. "We believe that 212Pb is the ideal radioisotope to realise the full therapeutic power of Targeted Alpha Therapy. This promise is strongly supported by preclinical results for 212Pb-ADVC001, which demonstrate the potential for best-in-class safety and efficacy."

"Patients with metastatic prostate cancer continue to benefit from advances in radiopharmaceutical treatment options," said Ken Herrmann, MD, AdvanCell Advisory Board member and Chair of the Department of Nuclear Medicine at the Universitätsklinikum Essen in Germany. "We are excited to be moving this 212Pb-based therapy forward in the TheraPb clinical study."

Since November 2020, AdvanCell has:

Developed the world’s first 212Pb-based Targeted Alpha Therapy to enter clinical trials in metastatic prostate cancer.
Invented proprietary platform technology that enables scalable manufacture of 212Pb, the ideal radioisotope to treat cancer.
Signed a letter of intent with a world-class radiopharmaceutical company to collaborate on a global 212Pb radioisotope and radioligand supply chain and drug manufacturing network.
Developed a proprietary target discovery and ligand development program encompassing a robust pipeline of Targeted Alpha Therapies to treat cancer.
Raised US $13M from world-class investors including Morningside and awarded $10M in non-dilutive grant funding,
Participated in the Cancer Lethality Lead Collaboration, which was awarded $10M from the Prostate Cancer Foundation’s TACTICAL Awards program, in collaboration with the Peter MacCallum Cancer Centre, Uniklinik Essen, University of California Los Angeles, and University of California San Francisco.
Built a 25-person world-class team across Australia and the United States and secured a 35,000-square-foot flagship manufacturing facility with plans to expand globally.

About 212Pb-ADVC001
212Pb-ADVC001 was designed to bind to PSMA, a clinically validated cell surface target highly expressed in prostate cancer. The proprietary drug candidate has been optimised for safety and efficacy and has demonstrated potential best-in-class attributes in preclinical studies.

About TheraPb Clinical Trial
The Phase I/II trial of 212Pb-ADVC001 is a multicentre, open-label study evaluating safety and efficacy in patients with PSMA-positive mCRPC. The trial’s primary objectives are to assess safety and tolerability and identify a recommended Phase II dose. Secondary objectives include measures of dosimetry, rPFS by RECIST and PSMA PET-CT, and PSA response. Multiple sites for the Phase I/II clinical trial of ADVC001 are now open for enrolment. For more information, visit clinicaltrials.gov (NCT05720130).

On November 7, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that 50 patients have now been imaged with 64Cu-SAR-Bombesin in its United States-based diagnostic trial, SABRE (NCT05407311)[1], for participants with PSMA-negative prostate cancer (Press release, Clarity Pharmaceuticals, NOV 7, 2023, View Source [SID1234637196]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

SABRE, which derives from "Copper-64 SAR-Bombesin in Biochemical Recurrence of prostate cancer" is a Phase II Positron Emission Tomography (PET) imaging trial of participants with PSMA-negative biochemical recurrence (BCR) of prostate cancer following definitive therapy. It is a multi-centre, single arm, non-randomised, open-label trial of 64Cu-labelled SAR-Bombesin. The primary objectives of the trial are to investigate the safety and tolerability of the product as well as its ability to correctly detect recurrence of prostate cancer.

Andrei Iagaru, MD, the Lead Principal Investigator for the trial, commented, "We are very excited to have successfully imaged 50 participants in the SABRE trial which further explores the clinical benefits of the innovative SAR-Bombesin product. Preclinical and clinical findings thus far indicate that SAR-Bombesin holds significant potential for improving the diagnosis and treatment of prostate cancer, giving hope to clinicians and patients who have no other suitable diagnostic options available. Being able to now visualise the gastrin-releasing peptide receptor (GRPr) expressing lesions with SAR-Bombesin has the potential to change the entire treatment paradigm for patients. With more tools to detect prostate cancer that may not be visible with other imaging agents, we may be able to better diagnose and offer more effective treatment for their disease.

"Unique to Clarity’s SAR Technology is the ability to image patients at later timepoints due to the optimal half-life of 64Cu. As such, 64Cu-SAR-Bombesin enables imaging not only on the day of product administration, but also at later timepoints, which may add utility to the diagnosis of cancerous lesions. We look forward to analysing data from the SABRE trial in hopes of continuing to validate the benefits associated with this agent and better managing the patients that have few options at present in the face of a devastating diagnosis."

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are pleased to have reached our recruitment target in our Phase II SABRE trial with the 64Cu-SAR-Bombesin imaging product. SAR-Bombesin has already resulted in improvements to the management of prostate cancer for patients with PSMA-negative or low PSMA expressing lesions through our clinical program. We believe this product has immense potential, both as a theranostic and as a stand-alone diagnostic, as it targets GRPr, which is present in a number of cancers, potentially broadening its use beyond PSMA-negative prostate cancer.

"The successful C-BOBCAT and BOP investigator-initiated trials have already showed the utility of SAR-Bombesin and its potential to identify disease in some patient subgroups where conventional diagnostic imaging has failed. We look forward to reporting further data relating to the potential advantages of SAR-Bombesin and, subject to these results, moving this product into a registrational Phase III trial."

About SAR-Bombesin

SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the gastrin-releasing peptide receptor (GRPr) present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPr is found in up to 100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)[2-6]. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu-SAR-Bombesin and 67Cu-SAR-Bombesin are unregistered products. Individual results may not represent the overall safety and efficacy of the products. The data outlined in this announcement has not been assessed by health authorities such as the US Food and Drug Administration (FDA). A clinical development program is currently underway to assess the efficacy and safety of these products. There is no guarantee that these products will become commercially available.

About Prostate Cancer

Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide[7]. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of prostate cancer in the US and around 34,700 deaths from the disease[8].

Approximately 20% of prostate cancers with BCR are PSMA-PET negative[9-12]. These patients are therefore unlikely to respond to therapeutic PSMA-targeted products and currently have few treatment options available to them. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment.

On November 7, 2023 BioRay Pharmaceutical Co., Ltd. (hereinafter referred to as BioRay) reported that the first patient has been dosed in the Phase I Clinical trial of BRY812, a third-generation antibody-drug conjugate (ADC) targeting LIV-1 for the treatment of advanced malignant tumors (Press release, BioRay Pharmaceutical, NOV 7, 2023, View Source [SID1234637195]). The leading institution of this clinical trial is Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the principal investigators are academician Song Erwei and Professor Yao Herui.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

LIV-1, also known as SLC39A6 or ZIP6, is a multipass transmembrane protein belonging to the ZIP superfamily of zinc transporters, possesses zinc transporter and metalloproteinase activities. LIV-1 directly participates in the homeostasis metabolism of intracellular zinc ions, facilitating the transport of zinc ions from the extracellular space or intracellular organelles to the cytoplasm, influencing cell growth. To date, there are no approved drugs worldwide that target LIV-1, making BioRay’s BRY812 the first LIV-1 ADC in China and the second to enter clinical trials globally.

BRY812 uses the proprietary CysLink irreversible chemical conjugation technology platform and highly stable linker to conjugate the antibody with the toxin. BRY812 has shown significant tumor growth inhibition in preclinical studies, and demonstrated excellent anti-tumor activity that is potentially superior to similar drugs. Compared to other drugs of the same class, it exhibits higher circulation stability, effective release of the payload within the tumor while significantly reducing toxin shedding and exchange in serum. This provides BRY812 with a great safety profile and an improved therapeutic window. Furthermore, BRY812 can also induce immunogenic cell death (ICD) and enhance the anti-tumor effects of immunotherapies such as anti-PD-(L)1.

Dr. Zhu Wei, CMO of BioRay, stated, " The significant market potential of ADCs requires differentiation in the market competition and expanding coverage to a broader patient population. As the first domestic ADC targeting LIV-1 to enter clinical trials, BRY812 is expected to treat various advanced malignant tumors, meet more clinical medication needs, and provide more treatment options for patients."

On November 7, 2023 Akeso (9926.HK) reported positive results from an interim analysis of AK104-302 study, a randomized, double-blind, multicenter, phase III clinical study evaluating PD-1/CTLA-4 bispecific antibody, cadonilimab (开坦尼) in combination with capecitabine plus oxaliplatin (XELOX) compared to placebo plus XELOX for first-line treatment of unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC) (Press release, Akeso Biopharma, NOV 7, 2023, View Source;gastric-cancer-or-gastroesophageal-junc-301979956.html [SID1234637194]). The trial achieved its primary endpoint by demonstrating a statistically significant overall survival (OS) improvement. The Independent Data Monitoring Committee (IDMC) recommended the early submission of a supplemental new drug application (sNDA) for cadonilimab in this indication based on the interim analysis.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The interim analysis showed that cadonilimab plus chemotherapy significantly improved OS in the all-comer patients irrespective of PD-L1 status, compared to placebo plus chemotherapy, meeting the pre-defined efficacy criteria. The safety profile remained consistent with previous results, with no new safety signals identified. These data will be presented in future international academic conferences/journals.

Interim Analysis Highlight:

Cadonilimab combined with chemotherapy significantly reduces the risk of death in all-comer patients, including whose with PD-L1 CPS≥5 and PD-L1 CPS<5. The hazard ratios (HRs) for OS in patients with different PD-L1 status were superior to other disclosed PD-1 plus chemotherapy combination treatment.
The combination of cadonilimab and chemotherapy also demonstrated superior OS in patients with PD-L1 CPS<5 as well as PD-L1 negative, maintaining the excellent performance seen in the phase II study.
"We extend our sincere gratitude to all the investigators, participants, and patients who actively took part in the clinical trial," expressed Dr. Yu Xia, Founder, Chairman, President, and CEO of Akeso. " Thanks to your dedication and efforts, an estimated 500,000 gastric cancer patients in China may have access to a new bispecific IO drug combination therapy offering improved treatment efficiency and survival prospects. We will continue to adhere to the recommendations of IDMC, efficiently promote the study, and engage in proactive communication with China’s National Medical Products Administration (NMPA) regarding the marketing application of cadonilimab for this new indication. We eagerly anticipate the early approval of this innovative therapy for the benefit of patients."

ABOUT AK104-302

AK104-302 is a Phase III clinical trial evaluating the use of cadonilimab (which is the world’s first approved PD-1/CTLA-4 bi-specific antibody) in combination with XELOX as first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). This randomized, double-blind, multi-center study aims to assess the efficacy of cadonilimab plus XELOX compared to placebo plus XELOX in the intent-to-treat (ITT) population.

The AK104-302 trial represents the first Phase III clinical study of a PD-1/CTLA-4 bispecific antibody combined with chemotherapy for first-line treatment of gastric cancer. Approximately 60% of patients in the ITT population had a PD-L1 CPS＜5, a proportion comparable to real-world scenarios.

About Cadonilimab

Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and improve safety while achieving anti-tumor efficacy.

The China National Medical Products Administration has approved cadonilimab for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase 3 study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer.

On November 7, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and The University of Texas MD Anderson Cancer Center reported a five-year strategic research collaboration agreement to evaluate zanidatamab, Jazz’s investigational HER2-targeted bispecific antibody, in multiple HER2-expressing cancers (Press release, Jazz Pharmaceuticals, NOV 7, 2023, View Source [SID1234637193]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The collaboration will combine MD Anderson’s translational medicine and clinical research expertise with Jazz’s expanding oncology drug development capabilities to investigate the potential of zanidatamab as monotherapy and in combination with other treatments for patients with different tumor types and stages. This includes its possible applicability in early-stage breast cancer, treatment areas where other HER2-directed therapies have failed, cancers with varying degrees of HER2-expression, and potentially rare, tissue-agnostic cancers.

"Current data indicates that zanidatamab has anti-tumor activity in multiple HER2-positive solid tumors, including positive results from a pivotal clinical trial for patients with HER2-amplified biliary tract cancers," said Funda Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics at MD Anderson. "We are pleased to extend our research efforts with Jazz through this new collaboration, which aims to address significant unmet needs in HER2-expressing solid tumors and to look for safe and effective alternatives to chemotherapy in diseases like early-stage breast cancer."

MD Anderson has been instrumental in researching breakthrough cancer therapies and was a key contributor to early investigations exploring the use of zanidatamab against an actionable target in the treatment of multiple tumor types and the subsequent Phase II HERIZON-BTC-01 trial, which evaluated zanidatamab for patients with treatment-refractory HER2-amplified biliary tract cancers. Results presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting demonstrated durable responses and a confirmed objective response rate of 41%. The presentation was selected for the 2023 Best of ASCO (Free ASCO Whitepaper) program.

Jazz and MD Anderson will establish a joint steering committee to oversee the collaboration, which will fund multiple studies over its five-year term. Research under the collaboration is expected to begin in late 2023 or early 2024. This effort builds upon a previous strategic collaboration between Jazz and MD Anderson focused on hematologic malignancies.

"We think zanidatamab has best-in-class potential as a bispecific antibody utilizing biparatopic binding, which results in HER2 signal blockade, as well as immune-mediated cytotoxicity of HER2-expressing cancer cells. Zanidatamab has compelling anti-tumor activity across a broad range of HER2-positive cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "We look forward to continuing to collaborate with MD Anderson to further evaluate zanidatamab’s potential to be transformative to the current standard-of-care in multiple HER2-expressing cancers. We are dedicated to advancing new treatment options for patients and we believe in the power of collaboration to accelerate the pace of research in difficult-to-treat cancers where persistent treatment gaps remain."

About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and immune activation leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.