On January 13, 2022 Tempus, a leader in artificial intelligence and precision medicine, reported the commencement of an open label phase II study, in collaboration with GlaxoSmithKline (GSK) to evaluate the efficacy and safety of ZEJULA (niraparib), a poly (ADP-ribose) polymerase (PARP) inhibitor used for patients with advanced or metastatic solid tumors and a germline or somatic PALB2 mutation (Press release, Tempus, JAN 13, 2022, View Source [SID1234605468]). The study, titled "Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors" (the PAVO study, NCT05169437) is sponsored by Tempus and opened for enrollment on January 7, 2022.

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Patients with PALB2 mutations have been shown to be at an increased risk of being diagnosed with breast and pancreatic cancers1. Recent studies demonstrate that patients with metastatic breast and pancreatic cancers with germline PALB2 mutations have benefited from treatment with PARP inhibitors2. ZEJULA is an oral, once-daily PARP inhibitor approved by the FDA in 2017 for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Phase 3 clinical trials are underway to evaluate the efficacy and safety of niraparib alone or in combination in additional solid tumors, including breast and lung cancers.

The PAVO study applies an innovative, data-driven approach designed to accelerate and streamline study timelines, and the signal-seeking process for niraparib. Additionally, Tempus leveraged its multi-modal dataset to expedite the protocol development and intelligent site selection in under 60 days.

The PAVO study is designed to enroll solid tumor patients with germline or somatic PALB2 mutations. Tempus is leveraging its TIME Trial Program, a just-in-time network of providers, to support rapid patient identification, site activation, and clinical trial enrollment. Under the study protocol, every patient sequenced through Tempus’ genomic sequencing platform will be pre-screened for PALB2 somatic and germline mutations.

"For this collaboration, our data produced insights led to the design of a new trial that we can expedite through our robust diagnostic and just-in-time trial network," said Dr. Kimberly Blackwell, Chief Medical Officer at Tempus. "We look forward to working together to evaluate niraparib’s potential for other populations who could benefit from this treatment."

1Hofstatter, Erin W, et al. "PALB2 Mutations in Familial Breast and Pancreatic Cancer." Familial Cancer, U.S. National Library of Medicine, June 2011, View Source

2Reiss KA;Mick R;O’Hara MH;Teitelbaum U;Karasic TB;Schneider C;Cowden S;Southwell T;Romeo J;Izgur N;Hannan ZM;Tondon R;Nathanson K;Vonderheide RH;Wattenberg MM;Beatty G;Domchek SM; "Phase II Study of Maintenance Rucaparib in Patients with Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or palb2." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), U.S. National Library of Medicine, View Source

On January 13, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, and Helmholtz Munich (Helmholtz Zentrum München), reported a cooperation agreement for the clinical development of a radiopharmaceutical therapy candidate to treat malignant brain tumor glioblastoma (Press release, ITM Isotopen Technologien Munchen, JAN 13, 2022, View Source [SID1234605467]). ITM and Helmholtz Munich will collaborate to support an upcoming dose-escalation Phase I clinical trial with LuCaFab (ITM-31). LuCaFab is a CA XII-specific antibody Fab fragment targeting molecule, developed by Helmholtz Munich, radiolabeled with ITM’s medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu, EndolucinBeta). The planned multicenter investigator-initiated trial (IIT) will be led by the Westfälische Wilhelms-Universität Münster (University of Münster, Germany).

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Under the terms of the agreement, which formalizes an ongoing collaboration between ITM and Helmholtz Munich, ITM supports the logistics and supply of the clinical trial material and provides funding for the trial, which is designed for the treatment of up to 15 patients. ITM holds the exclusive option, which may be executed at any time, to license the compound, related worldwide patents and know-how for the manufacturing, use and application of LuCaFab from Helmholtz Munich under already agreed upon terms. The option also allows ITM to access and use trial data for research and commercial activities.

Steffen Schuster, CEO of ITM comments: "We are pleased to continue our collaboration with Helmholtz Munich and to further advance ITM’s clinical pipeline. Glioblastoma is among the most malignant and most difficult to treat cancers. A precise radionuclide therapy targeting an antigen highly expressed in glioblastoma, such as CAXII, may inhibit tumor growth after surgical removal. We are dedicated to clinically explore this opportunity for these patients who have such a high unmet medical need."

Reinhard Zeidler, Project Leader at Helmholtz Munich: "We believe that the combination of our tumor-specific targeting molecule and ITM’s medical radioisotope offers a new opportunity to improve the treatment of glioblastoma. After first encouraging studies with other radioisotopes in brain tumors, we expect ITM’s radioisotope lutetium-177 to have particularly favorable medicinal properties. Therefore, we look forward to initiating our collaborative clinical trial with the Departments of Neurosurgery and Nuclear Medicine at the University of Münster."

About Glioblastoma Multiforme

Glioblastoma is one of the most malignant types of primary brain tumors. It is a rare tumor, with about 3-5 new cases per 100,000 individuals per year.1 Even though surgery, chemotherapy, and radiotherapy have advanced over the last decade, resulting in a gradual improvement in the survival and quality of life of glioblastoma patients, the prognosis remains very poor.2 Glioblastoma is a complex tumor which is very difficult to treat. Surgery is rarely curative as the tumor cells infiltrate the surrounding tissue and the blood-brain barrier places a limitation on medical therapies. Even with macroscopic removal of the tumor and subsequent treatment with external beam radiation and chemotherapy, there is a risk that individual tumor cells will remain in the tissue and begin to grow again (relapse). More than 90% of tumor recurrences occur in the immediate vicinity of the primary tumor. Therefore, the treatment of the tissue surrounding the tumor is of great importance.

About LuCaFab (ITM-31)

Glioma cells can selectively express certain surface antigenic proteins such as carbonic anhydrase XII (CAXII), which are not found on healthy brain cells. Targeted molecules which specifically bind to the proteins can be produced to attack these antigens. This approach falls under the category of Targeted Radionuclide Therapy (TRT), an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule that can precisely recognize tumor cells and bind to tumor-specific entities such as receptors expressed on the cell surface. The radioisotope accumulates at the tumor site and decays, releasing a therapeutic amount of ionizing radiation, thereby destroying tumor tissue. Helmholtz Munich has developed a new antibody binding fragment (Fab) against the CAXII antigen, which has been optimized for the treatment of glioblastoma. ITM’s no-carrier-added lutetium-177 (n.c.a. 177Lu, EndolucinBeta) is coupled to the antibody in order to selectively target and irradiate tumor cells. The resulting compound, LuCaFab (ITM-31), is administered via intracavitary injection, meaning it is applied directly into the tumor cavity following the surgical removal of the tumor to attack residual cancerous cells that lead to recurrent disease. LuCaFab thus acts as a complementary, adjuvant therapy to the current standard of care approach to glioblastoma as it is designed to be applied after initial treatment to prevent future tumor growth.

On January 13, 2022 EDAP TMS SA (Nasdaq: EDAP) ("the Company"), the global leader in robotic energy-based therapies, reported the publication of positive pre-clinical results using intraoperative high intensity focused ultrasound (HIFU) ablation of the pancreas in the peer-reviewed journal Cancers (Press release, EDAP TMS, JAN 13, 2022, View Source [SID1234605466]).

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The paper, entitled, Intraoperative HIFU Ablation of the Pancreas Using a Toroidal Transducer in a Porcine Model. The First Step towards a Clinical Treatment of Locally Advanced Pancreatic Cancer, describes a pre-clinical study designed to assess the feasibility of using HIFU under Doppler guidance to treat the pancreatic parenchyma and tissues surrounding the superior mesenteric vessels in vivo, in an animal model.

Pancreatic adenocarcinoma is among the most aggressive of all cancers. Regardless of treatment, the overall 5-year survival rate for patients with locally advanced pancreatic adenocarcinoma ("LAPA") is less than 5%. A HIFU approach could help in the treatment of such pathology that is inaccessible by other known therapeutic methods. Apart from palliative chemotherapy, no other curative options have been proven effective for the treatment of LAPA.

During the study, HIFU treatments were performed using an intraoperative HIFU probe which caused irreversible tissue necrosis in only a few seconds by producing sufficiently strong heat in the focal area. This study is the first step toward the launch of a Phase I study to evaluate the safety and feasibility of such a HIFU approach in patients with LAPA and to further confirm these encouraging results.

"The possibility of treating the pancreas using HIFU holds great promise for the treatment of locally advanced pancreatic cancers. If clinically successful, chemotherapy followed by HIFU treatment could rapidly become a novel treatment option of LAPA," concluded the paper’s authors.

Marc Oczachowski, EDAP’s Chairman and Chief Executive Officer, said: "We are very excited with these pre-clinical results and the promise they demonstrate for HIFU as a viable treatment for pancreatic cancer and other severe pathologies with low overall survival rates and no effective treatment options. We are proud of the ongoing work of the EDAP research team, who, together with Inserm and Centre Leon Bérard, are advancing the development of HIFU to offer patients a potentially effective treatment alternative for these difficult to treat cancers."

The full text of the paper can be found here.

On January 13, 2022 Amplia Therapeutics Limited (ASX: ATX) ("Amplia", the "Company") reported a GMP* manufacturing run of its clinical-stage drug candidate AMP945 has been successfully completed (Press release, Amplia Therapeutics, JAN 13, 2022, View Source;[email protected] [SID1234605465]). This provides additional drug substance to support toxicology studies and Phase 2 clinical trials in pancreatic cancer and lung fibrosis which are scheduled to start during 2022.

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Amplia’s contract manufacturing organisation (CMO) has successfully completed the manufacture of a 2 kg GMP batch of AMP945 within budget and on time. Previously, the maximum batch size of AMP945 that had been manufactured was 1 kg, meaning that the Company has now demonstrated a doubling of the scale at which AMP945 can be manufactured under GMP conditions. During the recently completed manufacturing run, the Company also implemented improvements to the manufacturing process for AMP945 that will support its future clinical and commercial development. Of note, long-term stability testing data has shown that AMP945 can be stored for periods of more than 24 months without detectable deterioration, an outcome that further supports commercial development of AMP945.

Amplia’s CEO, Dr John Lambert commented that "The successful doubling of our manufacturing capacity for clinical-grade AMP945 and the implementation of manufacturing improvements are outstanding outcomes which have exceeded our initial expectations. As well as providing material for our near-term development programs, these improvements lay a strong foundation for the AMP945 data package that will be required for future regulatory applications and its commercial development."

The Phase 2 clinical trial of AMP945 in patients with pancreatic cancer remains on track to commence during the current quarter. In addition, the extended (3-month) toxicology studies required to support the Phase 2 clinical trial of AMP945 in patients with fibrotic lung disease are on schedule to commence in February 2022 as previously advised.

* GMP: Good Manufacturing Practice

This ASX announcement was approved and authorised for release by the CEO of Amplia Therapeutics.

On January 13, 2022 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune disease, reported that the first patient has been dosed in its Phase 1/2 clinical trial of RTX-224 for the treatment of patients with certain relapsed/refractory or locally advanced solid tumors, including non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial (bladder) carcinoma and triple-negative breast cancer (Press release, Rubius Therapeutics, JAN 13, 2022, View Source [SID1234605463]).

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"While our lead oncology product candidate, RTX-240, is designed to broadly stimulate the immune system by activating and expanding NK and CD8+ memory T cells, we expect RTX-224 to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and known responsiveness to checkpoint inhibitors," said Larry Turka, M.D., chief scientific officer and head of research and translational medicine of Rubius Therapeutics. "Given the mechanism of action of RTX-224 and totality of our preclinical data generated to date, we believe RTX-224 will be an effective treatment for select advanced solid tumors."

RTX-224 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BB ligand (4-1BBL) and interleukin-12 (IL-12) on the cell surface.

About the RTX-224 Phase 1/2 Clinical Trial
This is a Phase 1/2 open label, multicenter, multidose, first-in-human dose-escalation and expansion study to determine the safety and tolerability, pharmacokinetics, maximum tolerated dose and a recommended Phase 2 dose and dosing regimen of RTX-224 in adult patients with certain relapsed/refractory or locally advanced solid tumors including non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial (bladder) carcinoma and triple-negative breast cancer. The trial will also assess pharmacodynamic changes in immune cell populations relative to baseline and anti-tumor activity. The study will include a monotherapy dose escalation phase followed by an expansion phase in specified tumor types during the Phase 2 portion of the trial.