On July 28, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) and AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq: AZN) reported that they have initiated a Phase II study of ORPATHYS (savolitinib), an oral, potent, and highly selective small molecule inhibitor of MET, a receptor tyrosine kinase, in patients with advanced or metastatic MET amplified gastric cancer ("GC") or adenocarcinoma of the gastroesophageal junction ("GEJ"). The first patient was dosed on July 27, 2021 (Press release, Hutchison China MediTech, JUL 28, 2021, View Source [SID1234586918]).

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The Phase II trial is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and pharmacokinetics ("PK") of ORPATHYS in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy. The primary endpoint is objective response rate ("ORR") as assessed by an independent review committee. Other endpoints include 12-week and 6-month progression-free survival ("PFS") rates, median PFS, duration of response ("DoR"), disease control rate ("DCR"), median overall survival ("OS"), safety, PK and quality of life.

The Beijing Cancer Hospital is the lead institution of this study. The lead investigator is Dr Shen Lin. For more information, please see clinicaltrials.gov identifier: NCT04923932.

MET-driven gastric cancer has a very poor prognosis.[i] This trial follows multiple Phase II studies that have been conducted in Asia to study ORPATHYS in MET-driven gastric cancer patients, including VIKTORY.2 VIKTORY is an investigator initiated Phase II umbrella study in gastric cancer in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified gastric cancer. Patients whose tumors harbor MET amplification were treated with ORPATHYS monotherapy, reporting an ORR of 50% (10/20, 95% CI: 28.0, 71.9).

It is estimated that MET amplification accounts for approximately 4-6% of GC patients.[ii],[iii] The annual incidence of MET amplification GC is estimated to be approximately 24,000 in China.[iv]

About ORPATHYS
ORPATHYS is an oral, potent, and highly selective MET tyrosine kinase inhibitor ("TKI") that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

ORPATHYS is marketed in China for the treatment of patients with non-small cell lung cancer ("NSCLC") with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

In 2011, following its discovery and initial development by HUTCHMED, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialize ORPATHYS. Joint development in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of ORPATHYS in China. AstraZeneca is responsible for the commercialization of ORPATHYS in China and worldwide. Sales of ORPATHYS will be recognized by AstraZeneca.

ORPATHYS development in NSCLC
Phase II study of ORPATHYS monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – In June 2021, ORPATHYS was granted drug registration conditional approval by the National Medical Products Administration of China (NMPA) for MET Exon 14 skipping alteration NSCLC. The approval was based on the results of a Phase II study in China; results of this study were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020, and updated results were published in The Lancet Respiratory Medicine[v] in June 2021. At a median follow up of 17.6 months, ORPATHYS demonstrated an objective response rate ("ORR") of 42.9% (95% confidence interval [CI] 31.1-55.3) and median progression-free survival ("PFS") of 6.8 months (95% CI 4.2-9.6) in the overall trial population. PFS was clinically meaningful across subgroups, and ORR results were consistent regardless of prior treatment or tumor histology, including in patients with the pulmonary sarcomatoid carcinoma (PSC) subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC subtypes (44.4%, 95% CI 29.6-60.0). Disease control rate ("DCR") in the overall trial population was 82.9% (95% CI 72.0-90.8). The safety and tolerability profile of ORPATHYS was consistent with previous trials, and no new safety signals were identified. Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population (NCT04923945).

SAVANNAH Phase II study of ORPATHYS in combination with TAGRISSO in patients who have progressed following TAGRISSO due to MET amplification or overexpression (NCT03778229) – This is a single-arm, open-label, global study in epidermal growth factor receptor ("EGFR") mutation positive NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with TAGRISSO, an EGFR TKI owned by AstraZeneca.

Phase III study of ORPATHYS in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (in planning) – This is a randomized, open-label study in China in EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

Phase III study of ORPATHYS in combination with TAGRISSO in treatment naïve patients with EGFR mutant positive NSCLC with MET overexpression (in planning) – This is a randomized, blinded study in China in untreated, unresectable or metastatic patients with EGFR mutation positive NSCLC with MET positive tumors.

ORPATHYS development in kidney cancer
SAVOIR randomized, controlled study of ORPATHYS monotherapy in MET-driven papillary renal cell carcinoma ("RCC") (NCT03091192) – In May 2020, data from 60 patients in this global study of ORPATHYS monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at the ASCO (Free ASCO Whitepaper) 2020 Program and published simultaneously in JAMA Oncology[vi]. ORPATHYS demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no ORPATHYS responding patients experiencing disease progression at data cut-off, and an encouraging overall survival ("OS") hazard ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with median not reached at data cut-off.

CALYPSO Phase I/II study of ORPATHYS in combination with IMFINZI PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of ORPATHYS in combination with IMFINZI, a PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the ORPATHYS/IMFINZI combination in patients with papillary RCC and clear cell RCC. An analysis of 41 patients enrolled in the PRCC cohort of in this study was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting[vii], showing a confirmed response rate in 14 MET-driven patients of 57%, with a median duration of response ("DoR") of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.

Phase III study in combination with IMFINZI PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic PRCC (in planning) – Based on the encouraging results of the SAVOIR and CALYPSO studies, we intend to initiate a global Phase III, open-label, randomized, controlled study of ORPATHYS plus IMFINZI versus sunitinib monotherapy versus IMFINZI monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic PRCC.

ORPATHYS development in other cancer indications
ORPATHYS opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including non-small cell lung cancer, gastric cancer and colorectal cancer.

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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

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On July 28, 2021 Almac Clinical Technologies, a member of the contract and development organization, Almac Group, and THREAD, a technology and service provider enabling decentralized clinical trials (DCTs), and reported a strategic partnership (Press release, Almac, JUL 28, 2021, View Source [SID1234585447]). The market leaders will integrate their technologies to enable more efficient clinical trials that generate better outcomes.

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By integrating their proprietary technology platforms, Almac and THREAD will provide sponsors and contract research organizations (CROs) with a full range of tools to reduce the risk of trial delays. Almac’s IXRS solution and industry-leading services for randomization and clinical trial supply management will be available to THREAD customers and THREAD’s DCT solution will be available to Almac customers. The two companies will leverage single sign-on and application program interfaces (APIs) to integrate their technologies and automate DCT workflows across their respective platforms to:

• minimize duplicate data entry, particularly for research sites
• provide sponsors with integrated reports on trial progress
• preserve automation to ensure operational efficiency

Organizations interested in learning more can request more information here.

"We’re thrilled to be working with THREAD, an acknowledged leader in DCT technology," said George Tiger, vice president of Global Business Development, Almac Clinical Technologies. "As part of our growing Partnership and Alliance program, this specific partnership will enable us to offer an additional level of support to Almac clients as they seek to decentralize their clinical trials."

"A common pain point for research sites is the abundance of technologies they have to independently maintain for each clinical trial," said John Reites, chief executive officer of THREAD. "By integrating Almac within our comprehensive platform, sites and study teams will have a single DCT study experience. Almac is a longstanding global leader in clinical research, and we’re excited about this synergistic partnership."

On July 28, 2021 National Resilience, Inc. (Resilience) and bluebird bio, Inc. (NASDAQ: BLUE), reported a strategic alliance aimed to accelerate the early research, development and delivery of cell therapies (Press release, bluebird bio, JUL 28, 2021, View Source [SID1234585446]). As part of the agreement, Resilience will acquire bluebird’s Research Triangle (bRT) manufacturing facility located in North Carolina and retain all of the more than 100 highly skilled technical staff and administrators currently employed at the site. Resilience will continue to support vector supply for both bluebird bio and 2seventy bio, bluebird’s spin-off oncology cell therapy company that is expected to launch by the end of 2021. The two companies are also finalizing a definitive agreement to establish partner programs that will share expense and revenue for successful commercialized oncology products and in parallel establish a next-generation manufacturing R&D collaboration.

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The 125,000-square foot facility, located in Durham, North Carolina, is currently manufacturing lentiviral vector (LVV), a critical component for cell and gene therapies. The facility includes drug substance and drug product production suites, quality control testing laboratories and warehousing space as well as additional footprint for future expansion. Resilience will continue to invest in the advancement of new technologies and expand the workforce as part of the company’s mission to build a digitally connected, end-to-end biomanufacturing ecosystem. Upon completion of the acquisition, the Resilience network will include 10 sites in North America with more than 1 million square feet of manufacturing, development, and support space.

In consideration for the acquisition of the bRT facility upon the closing of the transaction, bluebird will receive $110 million from Resilience. bluebird and 2seventy will continue to benefit from flexible and guaranteed access to LVV manufacturing for their emerging pipeline programs and the facility will be the primary source of suspension LVV.

The two companies plan to collaborate on the next phase of 2seventy’s pipeline, each applying their respective innovations in cell therapy development and manufacturing through a risk-sharing model.

"This alliance supports our vision of innovative product participation business models and bluebird’s demonstrated leadership and expertise in the field of gene and cell therapy makes them an ideal partner for this next phase of growth," said Rahul Singhvi, Sc.D, Chief Executive Officer of Resilience. "Further, the acquisition of the bRT facility gives us an important strategic presence in the Research Triangle region with one of the largest and most technically advanced facilities focused exclusively on cell and gene therapy manufacturing. We look forward to working closely with bluebird as they continue to advance important therapies for patients."

"Our mission of developing the next generation of cell therapies requires a thoughtful balance of innovation from both a scientific, medical and regulatory perspective as well as manufacturing perspective. We believe Resilience is an optimal partner to help us achieve this mission as well as the ideal successor for the next phase of the bRT facility’s growth," said Nick Leschly, chief bluebird. "As we continue to pivot toward the planned separation of bluebird and 2seventy, this strategic partnership allows us to share risk, streamline our business operations, provide additional capital and importantly ensures uninterrupted access to vector supply as we develop additional transformative treatments."

The closing of the transaction will be subject to the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, the negotiation of certain definitive agreements and other customary closing conditions.