On July 4, 2023 Taiho Oncology Europe GmbH and Taiho Pharmaceutical Co., Ltd., reported that the European Commission has granted conditional marketing authorization for LYTGOBI (futibatinib) monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma (CCA) with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy (Press release, Taiho, JUL 4, 2023, View Source [SID1234633042]).

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CCA is an aggressive cancer of the bile ducts of the liver. While rare – in Europe, approximately 6.000-8.000 people are diagnosed with CCA1 – this disease is associated with poor outcomes and is growing in prevalence worldwide2, underscoring the need for new treatment options.

"Today is an important day for current and future patients with CCA as well as the healthcare providers who treat them," said Peter Foertig, MD, Vice President, Medical Affairs, Taiho Oncology Europe. "LYTGOBI is an oral molecularly targeted medication that may provide clinically meaningful outcomes for patients undergoing treatment for CCA."

Added John Bridgewater, MD, PhD, Investigator and Senior Author of the recently published FOENIX*-CCA2 pivotal trial in the New England Journal of Medicine: "FGFR2 fusions/rearrangements are one of the most frequent actionable alterations in CCA. As an irreversibly binding FGFR inhibitor, LYTGOBI targets FGFR in a unique way and offers new hope in a disease that, for me, has been among the most challenging to treat in my career." Professor Bridgewater is a Clinical Researcher and Medical Oncologist at University College London Cancer Institute and University College London Hospitals NHS Foundation Trust.

The European Commission’s conditional marketing authorization for LYTGOBI is based on data from the aforementioned FOENIX-CCA2 trial, a global open label trial evaluating 103 patients with unresectable, locally advanced or metastatic intrahepatic (inside the bile ducts of the liver) CCA harboring FGFR2 gene rearrangements, including fusions.

In this trial, patients received LYTGOBI orally once daily at a dose of 20mg until disease progression or unacceptable toxicity. Within Europe, patients were enrolled from France, Germany, Italy, the Netherlands, Spain and the United Kingdom.

Results of FOENIX-CCA2 trial showed:

LYTGOBI demonstrated an objective response rate (ORR) of 42% as assessed by independent review (primary endpoint met).3
LYTGOBI demonstrated a median duration of response (DOR) – a key secondary endpoint – of 9.7 months. A total of 72% of the responses lasted >6 months.3
"I believe that LYTGOBI may be part of a new era in the treatment of CCA, one in which the power of personalised medicine may touch the lives of patients in ways we haven’t seen before with traditional chemotherapy," said Helen Morement, CEO of the AAMF – The Cholangiocarcinoma Charity and the UK’s only charity dedicated to this cause.

"We thank the many patients and healthcare professionals who participated in the FOENIX-CCA2 trial," said Atsushi Azuma, Managing Director of Taiho Pharmaceutical and Chairman of Taiho Oncology Europe. "Patients with CCA are often diagnosed at an advanced stage when surgery is not an option. We are pleased that LYTGOBI now will be a new treatment option for patients with CCA."

A conditional marketing authorization in Europe is granted for medicines that fulfill an unmet medical need to treat serious diseases, and the benefits of having them available earlier outweighs any risks associated with using the medicines while waiting for further evidence. Under the specific obligation to complete post-authorization measures for the conditional marketing authorization, Taiho has until October 2027 to provide additional clinical data on LYTGOBI.

Safety Information From the EU Summary of Product Characteristics (SmPC)3

LYTGOBI may cause serious adverse reactions. The most common serious adverse reactions were intestinal obstruction and migraine.

The most common adverse reactions were hyperphosphatemia, nail disorders, constipation, alopecia, diarrhoea, dry mouth, fatigue, nausea, dry skin, increased AST, abdominal pain, stomatitis, vomiting, palmar-plantar erythrodysaesthesia syndrome, arthralgia, and decreased appetite.

Prolonged hyperphosphatemia may cause soft tissue mineralization, including cutaneous calcification, vascular calcification, and myocardial calcification, anaemia, hyperparathyroidism, and hypocalcemia that may cause muscle cramps, QT interval prolongation, and arrythmias. Hyperphosphatemia is a pharmacodynamic effect expected with LYTGOBI administration. Recommendations for management of hyperphosphatemia include dietary phosphate restriction, administration of phosphate-lowering therapy, and dose modification when required.

LYTGOBI can cause serous retinal detachment, which may present with symptoms such as blurred vision, visual floaters or photopsia. Ophthalmological examination should be performed prior to initiation of therapy, 6 weeks thereafter, and urgently at any time for visual symptoms. For serous retinal detachment reactions, the dose modification guidelines should be followed.

LYTGOBI should not be used during pregnancy unless the clinical condition of the women requires treatment with LYTGOBI.

On July 4, 2023 Jacobio Pharma (1167.HK), a clinical-stage oncology company drugging the undruggable targets, reported its novel KRAS G12C inhibitor glecirasib’s pivotal study for pancreatic cancer has been approved from CDE (Center for Drug Evaluation), which became the first global pancreatic cancer registrational clinical study for KRAS G12C (Press release, Jacobio Pharmaceuticals, JUL 4, 2023, View Source [SID1234633041]).

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The pivotal clinical trial approved in China will evaluate the efficacy and safety of Glecirasib as a single agent for the second line treatment or above of Pancreatic Cancer patients with a KRAS G12C mutation. This is a multi-center, single-arm, open-label study. The study results will be used to submit NDA (New Drug Application) for pancreatic cancer.

"The pivotal study of pancreatic cancer is the second approved registrational study after non-small cell lung cancer", said gastrointestinal oncology expert Dr. Andrea Wang-Gillam, the Chief Medical Officer of Jacobio, "We hope to work with clinical study investigators to jointly advance the clinical trials and strive to bring more treatment options to cancer patients with KRAS G12C-mutated as soon as possible."

Pancreatic cancer is a malignant tumor and there is a lack of effective treatment currently. The five-year overall survival rate is only 5%. About 90% of pancreatic cancer patients have different types of KRAS mutations. Besides KRAS G12C inhibitor glecirasib, Jacobio is developing KRASmulti, KRAS G12D and other projects, which are expected to benefit more pancreatic cancer patients.

About Glecirasib
Glecirasib is Jacobio’s novel KRAS G12C inhibitor. Jacobio has initiated a number of Phase I/II clinical trials in China, the United States and Europe for patients with advanced solid tumors harbouring KRAS G12C mutation, including a pivotal clinical trial int NSCLC in China; a monotherapy study for STK11 co-mutated NSCLC in the front-line setting; combination therapy trials with SHP2 inhibitor JAB-3312, anti-PD-1 antibody and Cetuximab.

On July 4, 2023 Isofol Medical AB (publ) reported the conclusions from the company’s in-depth analysis of data from the Phase III study AGENT (Press release, Isofol Medical, JUL 4, 2023, View Source [SID1234633040]). The results from the analysis support the hypothesis that a different dose and administration regimen has the potential to improve the efficacy of the company’s drug candidate arfolitixorin. Isofol has therefore decided to continue the development of arfolitixorin and is intensifying preparations for a possible start of a minor clinical study.

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In preclinical and clinical studies, Isofol’s drug candidate arfolitixorin has shown the potential to improve the efficacy of the cancer drug 5-FU, which is part of the current standard treatment for colorectal cancer. However, the recent AGENT study did not show a statistically significant difference in efficacy between arfolitixorin and the standard treatment given in the control arm. Isofol therefore initiated a stepwise process in March 2023 to enable cost-effective and risk-minimizing continued development of the drug candidate arfolitixorin.

The process consists of three steps and Isofol has now completed the first step where the company has conducted an in-depth analysis of the available clinical data from the AGENT study. The aim has been to identify possible reasons why arfolitixorin in the AGENT study did not show any statistically significant difference in efficacy compared to the current standard of care. As part of the evaluation, the company, together with external experts, has also conducted PK (pharmacokinetic) modeling that calculate how drugs are absorbed, distributed and eliminated from the body.

The main conclusions of the evaluation in step 1 are:
The chosen dose and the administration regime of two bolus doses likely resulted in that the concentration of arfolitixorin in the patients’ blood was too low to deliver a sufficiently high amount of active substance into the tumor.
The consequence of the low dose, in comparison with the control group with standard treatment, was not justified because the control group was treated with a higher dose.
PK modeling and review of available safety data show that it is likely possible to administer arfolitixorin at a higher dose than that evaluated in the AGENT study and that a different dose and administration regimen could probably have improved the drug candidate’s efficacy.
Based on these conclusions, Isofol has decided to continue the development of arfolitixorin according to the previously communicated three-step process. Step two of the process has already been initiated with the Norwegian biotech company Oncosyne AS, which conducts preclinical tests in microtumors to document the effect of different doses. Results from these tests are expected after the summer.

In parallel, Isofol now intends to intensify the preparations to start a minor clinical study as soon as possible, in accordance with the third and final step in the company’s previously communicated strategy. However, a decision to start such a study will only be made when the results from step two are carefully analyzed.

Isofol continues to protect its financial position and carefully evaluates the results of each step of the strategic plan before allocating additional resources to the project. The company estimates that the planned activities will continue to be financed from existing funds.

On July 4, 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, ireported that it will be commencing a pivotal Phase III trial of its 64Cu SAR-bisPSMA diagnostic in prostate cancer (PC) following a successful end of phase meeting with the US Food and Drug Administration (FDA) (Press release, Clarity Pharmaceuticals, JUL 4, 2023, View Source [SID1234633029]). The trial will be named CLARIFY (Positron Emission Tomography using 64Cu SAR-bisPSMA in participants with high-risk PC prior to radical prostatectomy: A prospective, single-arm, multi-centre, blinded-review, Phase III diagnostic performance study) and is expected to begin patient recruitment in late 2023.

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The FDA is supportive of a prospective, non-randomised, single-arm, open-label, multi-center, Phase III diagnostic clinical trial of 64Cu SAR-bisPSMA PET in 383 participants with untreated, histopathology-confirmed PC, with high-risk features, who are proceeding to radical prostatectomy with pelvic lymph node dissection. As a pivotal trial, the final study results are intended to provide sufficient evidence to support an application to the FDA for approval of 64Cu SAR-bisPSMA as a new diagnostic imaging agent in PC.

The aim of the Phase III trial is to assess the diagnostic performance of 64Cu SAR-bisPSMA PET to detect PC within the pelvic lymph nodes. Evaluation will be across 2 imaging timepoints, Day 1 (day of administration) and Day 2 (approximately 24 hours post administration).

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are very excited to progress our Phase III trial and are appreciative of the time and valuable guidance the FDA has provided in relation to our 64Cu SAR-bisPSMA program during the end of phase meeting. The initiation of the CLARIFY trial is supported by compelling preclinical and clinical trial data. We would like to thank everyone who contributed to this exciting milestone, from our scientific collaborators at the University of Melbourne, who helped us overcome the low uptake and washout of first generation PSMA agents by assisting us in making an optimised PSMA agent for imaging and therapy, to the patients who participate in our clinical trials and to our incredible team and collaborators who work tirelessly towards our mutual goal of improving treatment outcomes for patients with PC. With this product, in both our diagnostic and therapy trials, we are now getting very close to achieving this goal.

"The positive results from our completed PROPELLER1 trial showed that 64Cu SAR-bisPSMA is safe, and its uptake in PSMA-expressing cancer lesions was significantly higher compared to the approved standard-of-care PSMA imaging agent for PC in Australia and the US. This may enable diagnosis of additional and smaller lesions, especially when coupled with the opportunity for delayed imaging, a characteristic not available to the first generation of PSMA imaging agents that exhibit high specificity but low sensitivity in diagnosing metastases outside of the prostate. Furthermore, we believe that the additional shelf-life of up to 48 hours could not only allow clinics greater flexibility in scheduling of the scans, but also improve patients’ access to care in clinics and geographic areas where the short half-life of current PSMA PET tracers restricts the use of radiopharmaceuticals. We look forward to opening our Phase III trial later this year to confirm and build on the positive data we have seen on the 64Cu SAR-bisPSMA product to date. Our hope is that better diagnostic tools will help clinicians determine the best course of treatment for their patients, informing a potential life-changing decision between the surgical removal of the prostate and other treatment options that may support a better quality of life post-treatment. We are excited about further exploring these clinical benefits as well as the logistical and manufacturing advantages of our Targeted Copper Theranostics (TCTs) platform and bringing this next generation PSMA diagnostic to PC patients around the world."

About SAR-bisPSMA
SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA binding motifs to Clarity’s proprietary sarcophagene (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-bisPSMA is a 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-bisPSMA and 67Cu SAR-bisPSMA are investigational products and not yet approved by health authorities.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide2. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of PC in the US and around 34,700 deaths from the disease

On July 3, 2023 CANbridge Pharmaceuticals, Inc. (1228.HK), a global biopharmaceutical company, with a foundation in China, committed to the research, development and commercialization of transformative therapies to treat rare diseases and oncology, reported that, based on the interim analysis recommendation of the independent data monitoring committee, it plans to continue the ongoing Phase 2 study of CAN008 in patients with newly diagnosed glioblastoma multiforme (GBM) in China to completion (Press release, CANbridge Life Sciences, JUL 3, 2023, View Source [SID1234633035]).

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"We are pleased that the independent data monitoring committee made the recommendation to continue the CAN008 Phase 2 glioblastoma multiforme trial in China, based on their analysis of the interim data," said James Xue, Ph.D., founder, chairman and CEO of CANbridge Pharmaceuticals Inc. "Glioblastoma is an intractable cancer with poor patient outcomes under standard-of-care. We look forward to continuing to develop CAN008 as a potentially new treatment for patients in China."

About the CAN008 Phase 2 Trial in glioblastoma multiforme (GBM)

The Phase 2 double-blinded study enrolled 119 subjects who were randomized 2:1 to receive intravenous CAN008 400 mg or placebo, in addition to standard-of-care chemoradiotherapy. All subjects underwent surgical excision of the GBM tumor prior to treatment. During the course of the study, they receive a 6-week course of triple therapy(temozolomide, radiotherapy and CAN008 or placebo), followed by a 1-month rest, then a 12-month course of dual therapy (temozolomide and CAN008 or placebo), and then monotherapy (CAN008 or placebo) until progression of disease, intolerability to treatment, death, or withdrawal. The primary endpoint is progression-free survival (PFS), and the secondary endpoint is overall survival (OS).

About CAN008

CAN008 (asunercept) is a CD95-Fc fusion protein that binds to the CD95 ligand and blocks the interaction between the ligand and the endogenous CD95 receptor. CAN008 has a unique dual mechanism of action, inhibiting both the invasive growth and migration of tumor cells, as well as T-cell apoptosis, which enhances immune recognition of the cancer. Earlier asunercept glioblastoma multiforme (GBM) clinical trial data showed favorable safety and tolerability, prolonged survival and improved quality-of-life.

Asunercept has been granted US FDA Orphan Drug Designation and Orphan Medicinal Product Designation by the European Medicines Agency (EMA) for GBM. It has also been accepted into the EMA’s PRIME (Priority Medicines) program, which provides support to medicines that could address unmet medical needs. In China, CAN008 has been classified as a Class 1 New Drug by the National Medical Products Administration. CANbridge holds the rights to develop and commercialize CAN008 for any indication in Greater China and is currently conducting a CAN008 Phase 2 trial in GBM in China.