On May 10, 2021 Chugai Pharmaceutical Co., Ltd. (Head office: Tokyo; President & CEO: Osamu Okuda; "Chugai") and SBI Pharmaceuticals Co., Ltd. (Head office: Tokyo; Representative Director & President: Yoshitaka Kitao; "SBI Pharma") reported that the companies decided to terminate the license agreement for the photodynamic diagnostic agent "ALAGLIO Divided Granules 1.5g ("ALAGLIO")" and that Chugai will consequently discontinue marketing of the product (Press release, Chugai, MAY 10, 2021, View Source [SID1234579497]).

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Both companies entered into a license agreement for ALAGLIO on March 13, 2017 which granted Chugai exclusive marketing rights of ALAGLIO in Japan. SBI Pharma obtained regulatory approval for ALAGLIO on September 27, 2017 for the indication of diagnostic agent to visualize non-muscle invasive bladder cancer at the operation of its transurethral resection, and Chugai launched the product on December 19 after the product had been listed on the National Health Insurance reimbursement price list on November 22.

Chugai will discontinue marketing and information provision for ALAGLIO on May 31, 2021. SBI Pharma will announce how these activities will be conducted from June 1, 2021.

Chugai and SBI Pharma will corporate to accomplish a smooth transition and maintain promotion of proper use of the product during the transition period.

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

On May 9, 2021 Grand Pharmaceutical and Healthcare Holdings Limited reported that the core product SIR-Spheres Y-90 resin microspheres of Sirtex Medical Pty Ltd ("Sirtex"), an associate company of the Group, has been successfully completed the first patient administration recently, following the approval by the US Food and Drug Administration ("FDA") to conduct a clinical trial for hepatocellular carcinoma ("HCC") (Press release, Grand Pharmaceutical, MAY 9, 2021, View Source [SID1234653971]).

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Sticking to patients-centered and innovation-driven, the Group will continue to expand its strategic planning in anti-tumor field and increase its investment in the world-class innovative products in the fields of radiopharmaceuticals and precision interventional therapy. The Group will continue to introduce world-class innovative products for different cancer indications in response to unmet clinical needs and enrich product pipeline and improve supply chain, dedicating itself into building world-leading radiopharmaceuticals platform and anti-tumor platform integrating diagnostics and treatment. The Group adopts the strategy of "global expansion and dual-cycle operation", forming a new pattern of domestic and international cycles that synergize with each other.

The SIR-Spheres Y-90 resin microspheres clinical study, DOORwaY90, is being conducted in the United States to evaluate the safety and efficacy of SIR-Spheres Y-90 resin microspheres as a first-line treatment for patients with unresectable or inoperable HCC patients in order to obtain approval for the HCC indication in the United States. The study will be conducted at 15 oncology centers, led by MD Anderson Cancer Center, and will enroll 100 patients in an open-arm study. The primary clinical endpoints will be the overall response rate (ORR) and duration of response (DoR). DOORwaY90 will be the first U.S. registration trial to utilize and delineate personalized dosimetry treatment planning and to define actionable post-treatment dosimetric verification for endpoint assessment, further providing high-quality supporting data for the use of SIR-Spheres Y-90 resin microspheres in HCC patients to benefit more HCC patients.

SIR-Spheres Y-90 resin microspheres is a targeted internal radionuclide product for liver malignant tumors, applying the world’s leading interventional technology is used to inject SIR-Spheres Y-90 resin microspheres into the blood vessels of liver tumors and release high-energy beta radiation to kill tumor cells. In 2002, this product was approved by the U.S. FDA for the treatment of unresectable colorectal cancer liver metastases (mCRC) based on the pivotal research CRI9101 (n=74), and in the same year it was approved by the European Union for the treatment of unresectable advanced liver malignancies.

SIR-Spheres Y-90 resin microspheres have been given to over 100,000 people in over 50 countries and regions around the world. With its remarkable clinical efficacy, it is recommended for treatment of hepatic malignant tumors by many authoritative guidelines, including National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper). It is also covered by medical insurance in places such as the United States and Europe. In addition, it is included in the Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 edition) and Chinese Guidelines for the Diagnosis and Comprehensive Treatment of Colorectal Cancer Liver Metastasis (2018 edition) , delineating clear clinical demands.

The registration of SIR-Spheres Y-90 resin microspheres in China is progressing smoothly. In August 2020, the National Medical Products Administration of the PRC was approved to file the new drug application for the treatment of colorectal liver metastases based on clinical trial data obtained overseas. The new drug application was accepted in November, 2020.

The Board of China Grand Pharmaceutical and Healthcare Holdings Limited, commented, "The successful completion of the first patient administration of SIR-Spheres Y-90 resin microspheres is an important progress made by the Group in the field of tumor treatment, laying the foundation for benefiting more liver cancer patients worldwide in the future. Looking ahead, the Group will make full use of its domestic industrial advantages and research and development capabilities, to accelerate commercialization process for innovative products and provide cancer patients with more advanced and diverse treatment options in the world."

On May 8, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca reported that New data from datopotamab deruxtecan (Dato-DXd), a TROP2 directed DXd antibody drug conjugate (ADC), showed preliminary response and disease control in patients with metastatic triple negative breast cancer (TNBC) with disease progression following standard treatment (Press release, Daiichi Sankyo, MAY 8, 2021, View Source [SID1234579499]).

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These preliminary data from the TNBC cohort of the TROPION-PanTumor01 phase 1 study were presented as a late-breaking mini oral presentation (Abstract #LBA4) at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Virtual Congress (#ESMOBreast21).

TNBC accounts for approximately 10 to 15% of breast cancer cases and is associated with higher disease recurrence and worse prognosis compared to other breast cancer subtypes.1,2,3 It is estimated that only 12.2% of patients with metastatic TNBC survive five years and median overall survival is generally less than two years.2,3

The preliminary objective response rate (ORR), assessed by blinded independent central review, was 43% in 21 evaluable patients treated with datopotamab deruxtecan [6 mg/kg (n=19) or 8 mg/kg (n=2)]. Five confirmed complete or partial responses (CR/PRs) were seen, with four additional CR/PRs awaiting confirmation at the time of data cut-off of January 8, 2021. A disease control rate of 95% was observed.

"There are currently limited treatment options for patients with previously treated metastatic triple negative breast cancer, historically a very difficult-to-treat subtype of breast cancer," said Aditya Bardia, MD, MPH, Director of Breast Cancer Research, Mass General Cancer Center, Harvard Medical School. "These initial safety and efficacy results of datopotamab deruxtecan in patients with triple negative breast cancer are encouraging and warrant further development for patients with breast cancer."

The safety profile of datopotamab deruxtecan seen in the TNBC cohort is consistent with safety that has been previously reported in the non-small cell lung cancer (NSCLC) cohort of TROPION-PanTumor01. No patients discontinued treatment due to adverse events (AEs); however, dose reductions due to AEs occurred in six patients (25%) and were most commonly due to stomatitis (13%) and mucosal inflammation (8%). Grade 3 or higher treatment emergent adverse events (TEAEs) regardless of causality occurred in 33% of patients. TEAEs grade 3 or higher included stomatitis (13%), fatigue (4%) and anemia (4%) with no grade 3 or higher TEAEs of diarrhea or neutropenia. The most common TEAEs overall in ≥25% of patients were stomatitis, nausea, fatigue, vomiting, and alopecia. No cases adjudicated as drug-related interstitial lung disease (ILD) were observed.

"These preliminary results provide proof-of-concept that targeting TROP2 with datopotamab deruxtecan may be an effective treatment strategy for patients with previously treated metastatic triple negative breast cancer," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "We are encouraged by the early tumor responses and disease control seen in these patients and we will continue to explore the potential of datopotamab deruxtecan in several types of breast cancer, including triple negative breast cancer."

"Triple negative breast cancer is known to be particularly aggressive and fast growing, and after treatment the risk of recurrence is faster and higher than in any other breast cancer subgroup," said Cristian Massacesi, Senior Vice President, Head of Late Stage Development Oncology R&D, AstraZeneca. "The preliminary results for datopotamab deruxtecan in this cohort of pretreated patients are encouraging for this high-potential targeted ADC."

Patients were treated with a median of four prior lines of therapy (range, 1-9, including prior lines of therapy in the [neo]adjuvant or metastatic setting) with a majority (88%) receiving more than two previous lines of treatment, including a taxane (83%), platinum-based chemotherapy (50%), immunotherapy (33%), sacituzumab govitecan (8%) and a PARP inhibitor (4%). As of data cut-off on January 8, 2021, 75% of patients remained on treatment with datopotamab deruxtecan.

Summary of TROPION-PanTumor01 Results

Efficacy Measure

Total Evaluable in TNBC Cohort (N=21)i, ii

ORR, %iii, iv

43% (n=9)

CR/PR (confirmed)

n=5

CR/PR (pending confirmation)

n=4

DCR, %v

95% (n=20)

PD, %

5% (n=1)

CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response

i Includes response evaluable patients who had ≥1 postbaseline tumor assessment or discontinued treatment. Postbaseline tumor assessments were not yet available for 3 patients at the data cutoff. One patient was not confirmed to have a target lesion per BICR and therefore had a best overall response of non-CR/non-PD.

ii Includes 2 patients that received 8 mg/kg datopotamab deruxtecan prior to selection of the 6-mg/kg dose for dose expansion.

iii Includes patients with a best overall response of CR, PR, stable disease, or non-CR/non-PD.

iv ORR is CR+PR; Responses are confirmed (CRs/PRs; n=5) plus those ongoing CRs/PRs too early to be confirmed (n=4).

v DCR is CR+PR+SD.

About TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicenter phase 1 trial designed to evaluate the safety, tolerability and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumors refractory to or relapsed from standard treatment or for whom no standard treatment is available, including NSCLC, TNBC and hormone receptor positive (HR+) breast cancer.

The dose escalation part of the study assessed the safety and tolerability of increasing doses of datopotamab deruxtecan to determine the maximum tolerated dose and/or recommended dose for expansion in patients with unresectable advanced NSCLC. The dose expansion part of the study further assessed the safety and tolerability of datopotamab deruxtecan at selected dose levels (4 mg/kg, 6 mg/kg and 8 mg/kg) in patients with NSCLC. Based on the preliminary efficacy and safety, the 6 mg/kg dose has been identified as the recommended dose for the NSCLC cohort.

The TNBC cohort was added in July 2020 and is currently evaluating patients with metastatic TNBC receiving datopotamab deruxtecan (6 mg/kg) with disease relapse or progression with standard treatment. The HR positive/HER2 negative cohort was added in March 2021 and is currently evaluating patients with metastatic HR positive/HER2 negative breast cancer receiving datopotamab deruxtecan (6 mg/kg) with disease relapse or progression with standard treatment.

Safety endpoints include dose limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DCR, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.

About TROP2 in Triple Negative Breast Cancer
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is overexpressed in several types of solid tumors, including breast cancer.4 Research indicates that high TROP2 expression is associated with cancer cell growth and proliferation and poor patient survival.4,5 While TROP2 is expressed across all breast cancer subtypes, it is overexpressed in approximately 80% of patients with TNBC, making it a promising molecular target for therapeutic development.5

Approximately 10 to 15% of patients with breast cancer are considered triple negative because the tumors test negative for estrogen, progesterone hormone receptors (HRs) and human epidermal growth factor 2 receptor (HER2).1,2,6 An estimated 260,000 new cases of TNBC were reported globally in 2018 with it being more common in younger women and those who are Black.1,2,7 Compared to patients with other breast cancer subtypes, prognosis for patients with metastatic TNBC is generally worse and the disease is more likely to recur following treatment with initial chemotherapy.1,3 Five-year survival of metastatic TNBC is estimated at 12.2% and median overall survival is generally less than two years.2,3

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is a TROP2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform.

A comprehensive development program called TROPION is underway globally with trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple solid tumors, including NSCLC, TNBC and HR+ breast cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.

On May 8, 2021 Daiichi Sankyo and partner AstraZeneca reported that next-gen antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) has show glimmers of efficacy and a reasonable safety profile in its first data release in breast cancer (Press release, AstraZeneca, MAY 8, 2021, https://www.fiercebiotech.com/biotech/daiichi-sankyo-astrazeneca-s-5b-enhertu-follow-up-shows-early-signs-success-breast-cancer [SID1234579494]).

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Having already seen some positives in its non-small cell lung cancer test, which is further along, Daiichi and AstraZeneca published the first look at Dato-DXd in triple-negative breast cancer (TNBC) at a late-breaking mini oral presentation at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Virtual Congress conference Saturday.

Nearly one year ago, AZ agreed to pay $1 billion upfront over two years for ex-Japan rights to the drug, which works as an ADC that targets tumor-associated protein TROP2, plus another $5 billion in milestones.

The drug combines an antibody targeting TROP2 that’s conjugated using a stable linker with a potent topoisomerase I inhibitor payload. It has a lower drug-to-antibody ratio that Daiichi suggests should both boost cell-killing activity and limit side effects.

The deal for the drug was after the success of AZ’s $6.9 billion deal for Enhertu (trastuzumab deruxtecan) from Daiichi, penned back in 2019. Within a few months of AZ coming on board, that drug was approved for patients with previously treated HER2-positive breast and gastric cancer. Dato-DXd will not be matching that record, but its TNBC data out over the weekend have the Japanese pharma optimistic about its future.

The data are still early, just a phase 1 and in only 21 patients, and Daiichi was keen to stress that there is a far way to go show just how well its drug workscu and how safe it will be in a larger patient population.

But in an early peek, the TNBC cohort of the TROPION-PanTumor01 phase 1 trial saw an objective response rate, assessed by blinded independent central review, hit 43% in 21 evaluable patients treated with Dato-DXd.

Five confirmed complete or partial responses were also seen, with four additional CR/PRs awaiting confirmation at the time of data cutoff on Jan. 8, 2021. A disease control rate of 95% was also observed.

RELATED: Gilead splashes out $21B for Immmunomedics, keeping the pedal on new target weeks after AZ-Daiichi deal

No p-values have yet been assigned, but this favors well (with the many cross-trial comparison caveats abound) with what will likely be its main rival, Gilead/Immunomedics’ Trodelvy (sacituzumab govitecan-hziy), an antibody and topoisomerase inhibitor conjugate directed to the TROP-2 receptor, which has, among others, FDA approval in TNBC that has spread.

At ESMO (Free ESMO Whitepaper) 2020, Trodelvy showed an ORR of 35%, though this was a phase 3 with more patients, and it also saw overall survival with a median of 12.1 months versus 6.7 months for chemo. Future trials for Daiichi’s drug will look to assess its survival potential, a key weapon it will need for any approval, but the company saw reasons to be cheerful about its prospects from these data.

On the safety side there had been concerns about drug-related interstitial lung disease, which had been noted by analysts as being seen in earlier trials. Daiichi said no such ILD cases were seen in this test, though Gilles Gallant, Ph.D., senior vice president and global head, oncology development, oncology R&D at Daiichi, told Fierce Biotech that they could not say for sure that this was not an issue, and future trials are needed to find that answer.

It did see less instances of severe diarrhea than are usual with the tech it uses, though six patients did have to have dose reductions because of adverse events. Daiichi said that these were most commonly due to stomatitis (13%) and mucosal inflammation (8%). Grade 3 or higher treatment emergent adverse events, regardless of cause, occurred in 33% of patients. The most common adverse events overall were stomatitis, nausea, fatigue, vomiting, and alopecia. No-one left the test due to adverse events, however.

Gallant, who was cautious about the trial simply because of how early it is and the small number of patients, does believe the drug is best-in-class in terms of its construct which differs from the likes of Trodelvy.

On May 7, 2021 OCI reported thet the company has decided to invest in Panolos Bioscience, a domestic bio venture company with anticancer drug candidates and multifunctional recombinant protein technology (Press release, Panolos Bioscience, MAY 7, 2021, View Source [SID1234633686]).

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On the same day, OCI announced on the 26th that it had signed an investment contract worth 5 billion won with Panolos Bioscience. "Through this strategic partnership, we will be able to secure expertise in the field of anticancer drugs," said OCI President Kim Taek-joong.

Panolos Bioscience is developing new biological therapeutics by utilizing αARTTM (Anti-angiogenesis-based Artifact Re-targeting Tri-specifics platform), a multi-specific drug generation platform. OCI explained that it is a platform that can reduce the side effects of single-target protein therapeutics and has excellent potential for expanding new drug pipelines through multiple targeting.

”PB101”, a next-generation anti-cancer drug candidate based on the αART platform, is a candidate for all types of Vascular Endothelial Growth Factor (VEGF)2, which is excessively produced around cancer cells (VEGF-A, VEGF-B, Placental Growth Factor). factor) to inhibit the growth of cancer cells.

Unlike conventional VEGF-inhibiting drugs that target only a portion of VEGF, it blocks all delivery pathways to reduce drug resistance and increase efficacy. PB101 is currently in the state of development of a process capable of mass production. Panolos Biosciences aims to start preclinical 3 in May and enter phase 1 clinical trial in 2022.