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MedNess: bite-size biopharma and medtech news

30th June, 2021

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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Mirati Therapeutics’ Adagrasin nabs Breakthrough Therapy Designation from the FDA for KRAS+NSCLC
On 24th June, Mirati announced that its KRASG12C inhibitor, adagrasib (MRTX849) has been granted the Breakthrough Therapy Designation from the US FDA for treatment of KRASG12C mutation-positive NSCLC following prior systemic treatment. The designation is based on initial data from the Phase 1/2 KRYSTAL-1 trial.
Background: KRAS has remained a difficult therapeutic target for many decades and tumors harbouring KRAS mutations are associated with poor prognosis. Apart from efficacy, targeting KRAS also involves considerable safety issues. KRASG12C mutations are present in ~14% of NSCLC adenocarcinoma, 3-4% of CRC, and in subsets of various other tumors.
Details: Adagrasib is being evaluated in a Phase 1/2
KRYSTAL-1 study in 391 patients with advanced solid tumors harbouring KRASG12Cmutation including NSCLC following progression on prior immunotherapy and/or chemotherapy.
Data presented during the 2021 European Lung Cancer Conference demonstrated an ORR and DCR of 45% and 96%, respectively in 51 efficacy-evaluable (Phase 1/1b – 14, Phase 2 – 37) patients with 600 mg BID dosing. At a mFU of 3.6 months, mTTR was 1.5 months. Patients with active brain mets experienced 63% reduction in primary lung tumor accompanied by disappearance of active brain mets.
However, 32% had Grade ≥3 TRAEs with 4.5% TRAEs leading to treatment discontinuation.
Implications: Mirati Therapeutics plans to submit an NDA for accelerated approval of adagrasib in H2 2021. Earlier this month, Mirati
entered into a collaborative agreement with Zai Lab giving the latter exclusive commercialization rights in mainland China, Hong Kong, Macau and Taiwan. The deal will accelerate enrolment in pivotal studies of adagrasib.
The company is also evaluating adagrasib in a randomized Ph
3 KRYSTAL-12 confirmatory trial versus docetaxel in previously treated KRASG12Cmutated NSCLC, Ph 2 KRYSTAL-7 trial in combination with pembroliumab as frontline therapy in KRASG12C mutated NSCLC, Ph 1/2 KRYSTAL 2 trial in combination with TNO 155 (SHP2i) in KRASG12C mutated NSCLC and CRC, and Ph 3 KRYSTAL-10 trial in combination with cetuximab in KRASG12C mutated CRC.
Additionally, it plans to submit an IND for its KRASG12D inhibitor, MRTX1133, in 2022.
In May 2021, Amgen’s Lumakras became the first drug to receive approval in KRASG12C+ NSCLC. The confirmatory Phase III
CodeBreak 200 study is ongoing. Although Lumakras is the frontrunner, some analysts believe that adagrasib could “emerge as the winner in the monotherapy setting”.
Collated by : Shilpa Rawal, PhD
Drug Approvals
Orpathys approved in China for patients with lung cancer and MET gene alterations
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “This approval makes Orpathys the only targeted medicine approved for these biomarker-selected patients in China, and it adds another novel medicine to our already diverse lung cancer portfolio. We are proud that this first-ever regulatory approval of Orpathys is in China, where we have a long-standing commitment to improving patient outcomes and working with the right partners to achieve that goal. Alongside HUTCHMED, we look forward to the continued development of this medicine across a range of cancers where MET alterations and amplification are drivers of tumour growth and treatment resistance.”
Fosun Kite gains first CAR T-cell therapy approval in China
“In relapsed or refractory LBCL, current standard-of-care is associated with poor long-term outcomes, so we are pleased to offer this new hope of survival for patients in China who are in need of new therapeutic options,” said Terence O’Sullivan, Vice President, International Region at Kite. “Thank you to the dedicated healthcare professionals, patients and caregivers who worked with the team at Fosun Kite to make this treatment option available in China.”
Click here for more Drug Approvals
Regulatory News

Regulatory Applications for Oncology Treatment Investigational Combination of Aliqopa® (copanlisib) and rituximab Submitted in the U.S. and EU
“The U.S. and EU submissions of the novel combination of Aliqopa and rituximab bring us forward in advancing new treatment approaches and addressing unmet needs of patients with different types of relapsed iNHL,” said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer. “We are excited about the potential of this investigational combination therapy based on the findings from CHRONOS-3 and we look forward to working with global regulatory authorities.”

Outcome of FDA ODAC Meeting Reviewing Retifanlimab as a Treatment for Patients with Squamous Cell Carcinoma of the Anal Canal (SCAC) Announced
“While we are disappointed by the outcome of today’s ODAC vote, we will continue to work closely with the FDA as it completes its review of the BLA for retifanlimab,” said Lance Leopold, M.D., Group Vice President, Immuno-Oncology Clinical Development, Incyte. “Patients with advanced SCAC who have progressed after first-line platinum-based chemotherapy currently have no FDA-approved treatments available to them and face an extremely poor prognosis. We continue to believe that retifanlimab can provide an additional, much-needed option for these patients based on the favorable benefit/risk shown in our trial.”
 Click here for more Regulatory News
Trial Results
Ph 3 KEYNOTE-826 Trial Met Dual Primary Endpoints of OS and PFS in Patients With Persistent, Recurrent or Metastatic Cervical Cancer
“Despite progress with prevention and screening, cervical cancer continues to be a major health problem, often affecting younger and middle-aged women,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Women diagnosed with metastatic cervical cancer have a particularly poor prognosis, and there is an urgent need for new treatment options. KEYNOTE-826 is the first study to show positive results for immunotherapy in first-line persistent, recurrent or metastatic cervical cancer, and we look forward to sharing these findings at an upcoming congress and discussing them with regulatory authorities. We thank the patients, their caregivers and investigators for their participation in this important study.”
“This analysis of the dataset for the ongoing ARC-7 study revealed encouraging clinical activity for the anti-TIGIT domvanalimab-based combinations, and furthermore, that the anti-PD-1 zimberelimab monotherapy arm showed activity similar to that of marketed anti-PD-1 antibodies studied in this setting,” said Bill Grossman, M.D., Ph.D., Chief Medical Officer of Arcus. “Next steps are to complete enrollment in all our open domvanalimab studies, execute on our broader plans for Phase 3 studies for domvanalimab across multiple cancer types, and further explore combinations with domvanalimab and etrumadenant.”
Click here for more Trial Results 
Trial/Program Status
First participant dosed in pivotal Ph 3 talapro-3 combination study of talazoparib and enzalutamide in mCSPC
“The prognosis for men with advanced prostate cancer has significantly improved since the introduction of novel hormone therapies, but additional therapeutic options are needed for the approximately 25 percent of men with tumors harboring DNA damage response (DDR) gene mutations, who may have poorer outcomes,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “By combining enzalutamide, which has a proven clinical benefit in men with metastatic castration-sensitive prostate cancer, with talazoparib, our PARP inhibitor that is active in DDR-mutated cancer, we may be able to offer a new treatment option that targets the underlying genetic mechanisms associated with DDR-mutated mCSPC.”
First Patient enrolled in Ph 3 VERACITY Trial of Sabizabulin (VERU-111) in Metastatic Castration Resistant and Androgen Receptor Targeting Agent Resistant Prostate Cancer
“We are excited to begin enrolling patients in our open label Phase 3 VERACITY clinical trial,” said Mitchell Steiner, MD, Chairman, President and CEO of Veru Inc. “As we have previously reported, in the Phase 1b/2 clinical trial sabizabulin had significant evidence of tumor efficacy including PSA declines and responses as well as objective and durable tumor responses. Furthermore, sabizabulin was well tolerated without neutropenia. In fact, the safety profile of sabizabulin appears to be similar to what is reported in the package inserts for an androgen receptor targeting agent such as enzalutamide or abiraterone. If the Phase 3 is successful, sabizabulin could be the next ‘go to drug’ in the largest and growing unmet medical need in men who have metastatic castration resistant prostate cancer and who have developed progression of prostate cancer while being treated with an androgen receptor targeting agent, but prior to using IV chemotherapy.”
Click here for more Trial Statuses
MedNess Business
Onco-News
Blackstone Life Sciences, Cellex Cell Professionals, and Intellia Therapeutics Launch New CAR T-Cell Company
“Bringing together GEMoaB’s universal CAR-T platform with Intellia’s differentiated allogeneic T cell platform and CRISPR-based cell engineering provides a unique opportunity to move cell therapy technology to new heights. Our focus is on providing significantly safer and more efficacious treatments to patients who are suffering from hard-to-treat cancers and autoimmune diseases.” said Andrew Schiermeier, Ph.D., current Executive Vice President and Chief Operating Officer of Intellia.
AbbVie Exercises Right to Acquire TeneoOne and Lead Asset TNB-383B for the Potential Treatment of Relapsed or Refractory Multiple Myeloma
"Since the beginning of this partnership, we have been encouraged by the potential of TNB-383B as a promising new therapy for multiple myeloma, and our analysis of the Phase 1 data to date has allowed us to make this decision with confidence," said Michael Severino, M.D., vice chairman and president, AbbVie. "While other BCMA and CD3 bispecific therapies require weekly administration, the recommended Phase 2 dose of TNB-383B will investigate infrequent dosing of every 3 weeks for intravenous administration, which is an important treatment factor for people living with multiple myeloma."
Click here for more on mergers, acquisition and business news
Editors' Desk
Richa Tewari, PhD
Oncology News
Shilpa Rawal, PhD
Onco I-Analyse
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
BioPharma News
Debarati Banik
HealthIT
Darpan Chakraborty
Social Media Manager
Nisha Peter, PhD
Consulting Editor
Abhi Dey
Consulting Editor
Rinki Saha
BioPharma News
Managing Editor
Shalini Roy Choudhury
Genes and Therapy
Managing Editor
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Content Editors: Richa Tewari , Esha SehanobishRinki Saha ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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