On July 6, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that the Phase 2 study of praluzatamab ravtansine in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-non-amplified breast cancer (Arm A) met its primary efficacy endpoint of confirmed objective response rate (ORR) of greater than 10 percent by central radiology review (Press release, CytomX Therapeutics, JUL 6, 2022, View Source [SID1234616502]). Praluzatamab ravtansine is a DM4-conjugated, conditionally activated antibody-drug conjugate (ADC) targeting CD166 and is wholly owned by CytomX.

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As of the data cutoff on May 13, 2022, 47 patients unselected for CD166 expression with advanced HR+/HER2-non-amplified breast cancer were evaluable for the primary efficacy endpoint. The ORR by central radiology review was 15 percent. Clinical benefit rate at 24 weeks by investigator (CBR24), as defined in the protocol as any response (confirmed or unconfirmed) or stable disease for 24 weeks, was 40 percent; median progression-free survival was 2.6 months. All patients in Arm A were treated at the initial Phase 2 starting dose of 7 mg/kg administered every three weeks. Arm B did not pass protocol-defined futility boundary (ORR was less than 10%) in patients with advanced triple-negative breast cancer (TNBC) and enrollment into Arms B and C will be discontinued.

As of this data cut, the safety profile of praluzatamab ravtansine in Arm A was generally consistent with toxicities observed in Phase 1 and with the DM4 payload; namely, high-grade toxicities or toxicities resulting in dose modifications were predominantly ocular or neuropathic in nature. Thirty percent of patients discontinued treatment for an adverse event (AE). Grade 3+ ocular and neuropathic toxicities were 15 and 10 percent, respectively. Arm B evaluated both 7 mg/kg and 6 mg/kg in patients with TNBC. The toxicity profile of 7 mg/kg starting dose was consistent with Arm A. In the 6 mg/kg cohort, no patients discontinued treatment for an AE and Grade 3+ ocular or neuropathic related events were lower at 3, and 0 percent, respectively. Biomarker analysis is ongoing. CytomX intends to submit data from this study for presentation at a medical conference in the second half of 2022.

"These results from our Phase 2 evaluation of praluzatamab ravtansine support single-agent activity of this novel drug candidate in hormone receptor-positive breast cancer where significant unmet need remains," said Sean McCarthy, D.Phil., chief executive officer and chairman at CytomX Therapeutics. "However, we do not believe the median progression-free survival at 7 mg/kg supports further evaluation at this dose. While we are encouraged by the emerging safety profile of 6 mg/kg, we do not plan to further advance this program alone given current financial market conditions and will be seeking a partnership."

Kathy D. Miller, MD, Ballvé Lantero Professor of Oncology, Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana, and lead investigator of the Phase 2 study stated, "In this Phase 2 study, praluzatamab ravtansine showed single-agent activity in an unselected population of patients with advanced HR+/HER2-non-amplified breast cancer; additional clinical studies at 6 mg/kg are warranted."

Conference Call & Webcast
CytomX management will host a conference call and a simultaneous webcast today at 5:00 pm ET (2:00 pm PT) to discuss these results. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. A live webcast of the call can be accessed via the Events and Presentations page of CytomX’s website at View Source

About Praluzatamab Ravtansine
Praluzatamab ravtansine is a conditionally activated antibody-drug conjugate (ADC) comprised of a CD166-directed humanized monoclonal antibody conjugated to the maytansinoid DM4, a tubulin inhibitor. Praluzatamab ravtansine utilizes CytomX Probody platform technology, which incorporates a masking peptide to cover and block the cellular binding region of the antibody. Tethered to the antibody via a protease-cleavable linker, the masking peptide is designed to be removed in a protease-rich tumor microenvironment, enabling the ADC to be unmasked and engage its target to deliver the toxic DM4 payload inside tumor cells. The goal is to have praluzatamab ravtansine remain inert while in circulation to limit binding in healthy tissues until it is activated by tumor-associated proteases. Praluzatamab ravtansine was evaluated in a three-arm Phase 2 study (NCT04596150) in patients with hormone receptor-positive/HER2-non-amplified breast cancer and patients with triple-negative breast cancer.

About the Phase 2 Study of Praluzatamab Ravtansine in Breast Cancer (NCT04596150)
Arm A of the study evaluated praluzatamab ravtansine as monotherapy (7 mg/kg, Q3W) in patients with inoperable, locally advanced or metastatic hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-non-amplified breast cancer. Patients received 0 to 2 prior cytotoxic chemotherapies in the inoperable, locally advanced, or metastatic setting, regardless of the level of CD166 expression.

Arm B assessed praluzatamab ravtansine as a single agent (6 or 7 mg/kg, Q3W) in patients with inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC). Patients received 1 to 3 prior lines of chemotherapy for inoperable, locally advanced, or metastatic disease and had CD166 expression.

Arm C studied praluzatamab ravtansine (6 mg/kg, Q3W) in combination with pacmilimab (1200 mg, Q3W), CytomX’s proprietary conditionally activated anti-PD-L1 antibody, in patients with TNBC. Eligibility was the same as Arm B with the additional requirement that patients’ tumors were programmed death-ligand 1 (PD-L1)-positive by an FDA-approved test.

On July 6, 2022 Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus") reported that the United States Food and Drug Administration ("FDA") has accepted for review the Biologics License Application ("BLA") resubmission for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma ("NPC") and for toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy (Press release, Shanghai Junshi Bioscience, JUL 6, 2022, View Source [SID1234616501]).

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The FDA has set a Prescription Drug User Fee Act ("PDUFA") action date for December 23, 2022. The Agency earlier communicated that the review timeline for the BLA resubmission would be six months, as onsite inspections in China would be required. Travel restrictions related to the COVID-19 pandemic previously hindered the FDA’s ability to complete required inspections. Coherus plans to launch toripalimab in the United States in the first quarter of 2023, if approved.

"Although the COVID-19 pandemic has created tremendous challenges for everyone, our dedication to bring better treatment options to patients around the world remains steadfast," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "Through our concerted efforts with our partner, Coherus, we have made continual progress towards obtaining toripalimab’s first marketing authorization outside of China. Over the next several months, we will work closely with the FDA to facilitate the review of this novel drug."

"Toripalimab would address a critical unmet medical need for patients with nasopharyngeal carcinoma, an aggressive cancer for which there are currently no FDA-approved immunotherapy treatments. We collaborated closely with our partner, Junshi Biosciences, to complete the quality process changes requested by the FDA and facilitate the rapid resubmission of the toripalimab BLA," said Dr. Theresa LaVallee, Chief Development Officer of Coherus.

"For Coherus, the toripalimab resubmission is one of several key development and commercialization milestones we are sharply focusing on over the next twelve months, and we are pleased with the Company’s execution and progress on all of them," said Denny Lanfear, CEO of Coherus. "We now look forward to the August 2, 2022 target action date for our BLA for CIMERLI, our Lucentis biosimilar, followed by product launch which we are confident will be very successful. The toripalimab December 2022 PDUFA date follows directly, and the projected toripalimab launch in Q1 2023 will formally mark our entry into immuno-oncology, where Coherus will be one of just a handful of companies with a proprietary PD-1 as a foundation stone to build its oncology franchise upon. Lastly, twelve months from now, in July 2023, we expect to begin marketing our Humira biosimilar, YUSIMRY, which was approved by the FDA in December 2021. Preparations for that commercial launch are going very well. Biosimilar market execution is a demonstrated Coherus competency, and we believe that our commercialization strategy provides a robust framework against which we can successfully execute to meet our market expectations and share projections."

Following approval of toripalimab for NPC, Coherus’ strategy in the US includes evaluating toripalimab’s ability to deliver substantial clinical benefit in significant indications, in combination with other cancer drugs and immunotherapies, through co-development agreements.

About Toripalimab in NPC
NPC is a type of aggressive cancer that starts in the nasopharynx, the upper part of the throat behind the nose and near the base of skull. Due to the location of the primary tumor, surgery is rarely an option, and patients with localized disease are treated primarily with radiation and chemotherapy. In the United States, there are presently no immunotherapies approved for the treatment of NPC.

The toripalimab BLA is supported by the results from JUPITER-02, a randomized, double blind, placebo-controlled, international multi-center Phase 3 clinical trial, as well as POLARIS-02, a multi-center, open-label, pivotal Phase 2 clinical study. The JUPITER-02 results were first presented in June 2021 in a plenary session of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") annual meeting (#LBA2) and subsequently published in detail as the cover article of the September 2021 issue of Nature Medicine. The POLARIS-02 results were published online in January 2021 in the Journal of Clinical Oncology.

The FDA has granted Breakthrough Therapy designation ("BTD") for toripalimab in combination with chemotherapy (gemcitabine and cisplatin) for the 1st line treatment of recurrent, locally advanced or primary metastatic non-keratinizing NPC and for toripalimab monotherapy for patients with recurrent or metastatic non-keratinizing NPC with disease progression on or after platinum-containing chemotherapy. Additionally, the FDA has granted Orphan Drug designation for toripalimab for NPC.

In China, the National Medical Products Administration ("NMPA") in 2021 approved toripalimab for two NPC indications.

About Toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells. In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are five approved indications for toripalimab in China.

On July 6, 2022 Bio-Techne (NASDAQ: TECH), a global life sciences company providing innovative tools and bioactive reagents for the research and clinical diagnostic communities reported the European launch of the CE-IVD marked RNAscope ISH Probe High Risk HPV, intended for use in patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) to aid in the identification of high-risk human papillomavirus (HPV) (Press release, Bio-Techne, JUL 6, 2022, View Source [SID1234616500]).

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HPV is a major cause of OPSCC, and HPV has emerged as a valuable diagnostic marker that significantly impacts clinical management.1,2 Immunohistochemistry (IHC) for p16 protein, a surrogate marker, is widely used for HPV detection in OPSCC; however, misdiagnosis rates of 5‑20% have been reported when using p16.3 The presence of E6/E7 mRNA is considered the gold standard for diagnosing HPV-related OPSCC.4 RNAscope offers a superior method for detection of E6/E7 mRNA when assessing HPV status in OPSCC patients, enabling clinicians to provide a more accurate diagnosis and improve patient management.5

"Bio-Techne’s innovative tissue diagnostic solutions empower our customers to serve patients and improve lives," said Kim Kelderman, President, Diagnostics and Genomics Segment of Bio-Techne. "We are excited to launch the new CE-IVD RNAscope ISH Probe High Risk HPV, which provides pathologists a highly accurate tool for the direct detection of HPV mRNA to inform treatment selection in oropharyngeal squamous cell carcinoma patients."

RNAscope in situ hybridization (ISH) is a highly sensitive and specific spatial biology technology. Its double Z probe design enables an exceptional signal-to-noise ratio when staining formalin-fixed paraffin-embedded (FFPE) tissue specimens. RNAscope ISH allows users to visualize and localize biomarker expression patterns by light microscopy. Over the past 10 years, RNAscope ISH has proven its reliability, reproducibility, and robustness with more than 6000 peer reviewed publications, making it a powerful solution for anatomic pathologists.

RNAscope ISH Probe High Risk HPV is used in an RNAscope ISH assay for the qualitative detection of HPV E6/E7 mRNA in FFPE tissue specimens. RNAscope ISH Probe High Risk HPV is for use in clinical laboratories with the CE-IVD marked BOND RNAscope Brown Detection kit on the automated Leica Biosystems BOND-III stainer. The assay detects high-risk HPV types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82.

On July 6, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that the United States Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation (RPDD) to Kazia’s paxalisib for the treatment of atypical rhabdoid / teratoid tumors (AT/RT), a rare and highly-aggressive childhood brain cancer (Press release, Kazia Therapeutics, JUL 6, 2022, View Source [SID1234616497]).

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Key Points

Rare Pediatric Disease Designation (RPDD) is granted to drugs which are under development for rare childhood diseases.

RPDD means that the sponsor may be entitled to receive a pediatric priority review voucher (pPRV) if the drug is initially approved for that rare childhood disease. A PRV grants the holder an expedited six-month review of a new drug application. PRVs are tradeable and have historically commanded prices in excess of US$ 100 million.

FDA’s award of RPDD follows the presentation of promising preclinical data for paxalisib in AT/RT, which was presented by Professor Jeffrey Rubens and colleagues at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA, in April 2022.

Paxalisib was previously granted orphan drug designation (ODD) for AT/RT by FDA on 16 June 2022.

Kazia CEO, Dr James Garner, commented, "this is the second time that paxalisib has been granted RPDD, and it demonstrates the importance of childhood brain cancer in the overall paxalisib development program. Brain cancer is the most common cause of cancer death in children, and outcomes in many forms of childhood brain cancer have not improved in decades. We very much hope that paxalisib can make a difference to families affected by both DIPG and AT/RT, and we will be working closely with clinicians, researchers, and FDA to determine the optimal way to move the drug forward."

Rare Pediatric Disease Designation

The Food and Drug Administration Safety and Innovation Act (2012) established FDA’s RPDD initiative. RPDD may be granted to drugs in development for diseases which primarily affect children (under the age of 18 years), have an incidence of less than 200,000 new cases per annum in the United States, and which are serious or life-threatening.

A sponsor of a drug with RPDD may request a Rare Pediatric Disease Priority Review Voucher (PRV) at the time of a marketing application to FDA. In effect, the PRV shortens the FDA review period for a future marketing application of any drug from 12 months to 6 months. PRVs can be sold to other companies and have historically been transacted at prices in the tens to hundreds of millions of dollars. For a large company launching a billion-dollar drug, the six-month acceleration in regulatory review can be of substantial economic value. In 2019, five pediatric PRVs were granted by FDA.

Next Steps

A phase II clinical trial of multiple drug therapies, including paxalisib, is ongoing, under the sponsorship of the Pacific Pediatric Neuro-Oncology Consortium (PNOC) (NCT05009992). This study combines several investigational drugs in the treatment of patients with diffuse midline gliomas (DMGs), a category which includes DIPG. Initial data from this study is anticipated in CY2023.

A phase I study of paxalisib in DIPG, led by St Jude Children’s Research Hospital in Memphis, TN (NCT03696355), is nearing completion, and final data is expected to be submitted for publication by the end of CY2022.

On July 6, 2022 Cardinal Health (NYSE: CAH) reported that it has acquired the Bendcare group purchasing organization (CPO-GPO) entity and made a minority investment in the Bendcare management services organization (MSO) (Press release, Cardinal Health, JUL 6, 2022, View Source [SID1234616496]). Following the acquisition of the CPO-GPO, current Bendcare-affiliated CPO-GPO members will transition to Cardinal Health’s Cornerstone Rheumatology GPO, and Cardinal Health will be the exclusive distributor for those practices.

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This acquisition demonstrates Cardinal Health’s strategy of prioritizing investment in strategic growth areas and expands distribution opportunities and technology solution offerings for specialty practices. Financial terms of the transaction were not disclosed.

"Bendcare is a leader in delivering real-world technology, specialty practice management and research solutions that empower physicians and patients in the specialty rheumatology market," said Dan Duran, Senior Vice President and General Manager, Provider Solutions, Cardinal Health Specialty Solutions. "We are excited to combine their solutions with our best-in-class distribution to support rheumatology providers so they can ultimately focus on achieving cost-effective patient outcomes and care."

Combining the expertise and capabilities of Cardinal Health and Bendcare together will create an integrated suite of clinical, practice management and distribution solutions to help support the success of rheumatology practices nationwide.

"Rheumatology providers and patients are navigating a number of industry challenges," said Andrew S. Ripps, CEO, Bendcare. "Cardinal Health is an industry leader in distribution and technology solutions. Our synergistic cultures, combined with our service and technology innovation and expertise, will ignite our ability to continue to lead in the rheumatology space as we expand into other specialties and improve patients’ experience, care and value."

Cardinal Health has one of the largest healthcare supply chains in the U.S. with strategically located distribution centers that enable fast and efficient delivery anywhere in the U.S. Through Specialty Solutions, Cardinal Health provides reliable distribution and advanced technology solutions to community-based practices across the nation with specialties in rheumatology, oncology, urology, nephrology, gastroenterology, ophthalmology, neurology, immunology and multi-specialty infusion centers.