On January 19, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Zymeworks Inc. (Nasdaq: ZYME) reported tolerability and efficacy results, including the first overall survival (OS) data, from a Phase 2 trial examining zanidatamab, an investigational HER2-targeted bispecific antibody, in combination with chemotherapy, in first-line patients with HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA) (Press release, Jazz Pharmaceuticals, JAN 19, 2023, View Source [SID1234626405]).

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The preliminary results showed that, at the time of analysis, the median OS had not yet been reached with a median duration of study follow-up of 26.5 months. The 18-month overall survival rate was 84% [95% confidence interval (CI): 68%, 93%].

"Gastroesophageal adenocarcinoma represents one of the most frequent tumor types worldwide and, tragically, a leading cause of cancer-related deaths. Compared to what has historically been reported for OS with the current approved standard of care1, the OS findings from the combination of zanidatamab and chemotherapy in this trial are very compelling," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre. "HER2 has been recognized as a predictive biomarker for these cancers, and it is promising to see a treatment targeting this expression exhibit strong and durable anti-tumor activity when administered with chemotherapy."

"We are very encouraged by the data from this Phase 2 trial, which demonstrate zanidatamab administered with chemotherapy is a highly active treatment regimen and resulted in significant and durable tumor response in the first-line setting for patients with advanced HER2-expressing mGEA," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "These results showcase zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA, and we look forward to additional data in 2024 from the ongoing pivotal Phase 3 trial that may support U.S. and global regulatory filings."

Trial Results

The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with advanced HER2-expressing mGEA, which is comprised of gastric, esophageal and gastroesophageal junction (GEJ) patients. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with mGEA were enrolled from 15 sites across the United States, Canada and South Korea, and patients were administered zanidatamab with physician’s choice of chemotherapy treatment (standard first-line combination therapy).

The data demonstrated zanidatamab combined with standard chemotherapy is a highly active treatment regimen for first-line therapy of HER2-positive mGEA. In 42 patients evaluable for OS receiving zanidatamab in combination with chemotherapy, the 18-month OS rate was 84% (95% CI: 68%, 93%), the 12-month OS rate was 88% (95% CI: 73%, 95%), and the median overall survival had not yet been reached (with 26.5 months median duration of study follow-up). Treatment with zanidatamab resulted in a confirmed objective response rate (cORR) of 79% (95% CI: 63-90%), a disease control rate (DCR) of 92% (95% CI: 79-98%), with three patients achieving complete response among 38 response-evaluable patients.

The median duration of response was 20.4 months (95% CI: 8.3-NE) with a median progression-free survival (mPFS) of 12.5 months (95% CI: 7.1-NE) with 17 patients having an ongoing response at the time of data cutoff. The regimen was manageable, tolerable and consistent with the observed safety profiles reported for other standard combination regimens for patients with HER2-positive GEA.

Data were presented in a poster session entitled Zanidatamab + Chemotherapy as First-Line Treatment for HER2-expressing Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Gastrointestinal Cancers Symposium (ASCO GI) taking place in San Francisco. The presentation is available to conference registrants on the ASCO (Free ASCO Whitepaper) GI conference website (Abstract Number 347), and will be available to the general public on Zymeworks’ website.

Zymeworks continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA.

About Zanidatamab
Zanidatamab is an investigational bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks, along with collaborators Jazz and BeiGene, Ltd. (BeiGene), are developing zanidatamab in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Gastroesophageal Adenocarcinoma

Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients are HER2–positive.2,3,4 HER2–positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.

On January 19, 2023 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for LNS8801 for the treatment of patients with metastatic cutaneous melanoma (Press release, Linnaeus Therapeutics, JAN 19, 2023, View Source [SID1234626404]).

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The FDA’s Office of Orphan Drug Products grants orphan drug status to support drug candidates in development for underserved patient populations or rare disorders that affect fewer than 200,000 people in the United States. Orphan drug designation provides certain benefits, including market exclusivity upon FDA approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

"We are extremely pleased to have received orphan drug designation for cutaneous melanoma from the FDA. This is an important milestone that has emerged from the very promising data we have seen in biomarker-defined patients with metastatic cutaneous melanoma in our dose-expansion cohorts," commented Patrick Mooney, MD, CEO of Linnaeus. "We look forward to further opening a randomized controlled study in patients with treatment-refractory cutaneous melanoma to explore the promising results we have already seen with LNS8801 alone and also in combination with pembrolizumab."

Having completed dose escalation, Linnaeus is currently testing LNS8801 in its phase 1/2 adaptive-design clinical trial as a monotherapy and in combination with KEYTRUDA (pembrolizumab) in various cancers and patient populations.

About LNS8801

LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing clinical study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancers, and a predictive biomarker has been identified.

On January 19, 2023 Independent biopharmaceutical company Specialised Therapeutics Asia (ST) is pleased to reported that a new therapy to treat rare gastrointestinal stromal tumour (GIST) shown to improve survival has now been approved in New Zealand (Press release, Specialised Therapeutics Australia, JAN 19, 2023, View Source [SID1234626403]).

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The therapy, QINLOCK (ripretinib) has been approved for use by the country’s regulatory agency Medsafe for the treatment of adult patients with GIST who have received prior treatment with three or more kinase inhibitors, including imatinib.

It is currently being made available to eligible patients in New Zealand via a co-pay Access Program while it is considered by PHARMAC for reimbursement.

Cancer specialists said the approval was welcome news for NZ patients diagnosed with GIST.

In a joint statement, medical oncologists Dr Joanna Connor and Dr Clement Korenbaum from the Auckland City Hospital said QINLOCK would provide patients with more treatment options, aligning with international standard of care.

"QINLOCK offers clinically meaningful benefits in progression free and overall survival for patients living with advanced GIST," they noted. "It offers an option for patients who have progressed on other treatments."

"We would now support having fully funded access to QINLOCK for all those affected by advanced GIST who meet the pivotal study’s criteria."

61-year-old Auckland grandfather and sales manager Tom Turrall was diagnosed with GIST earlier this year after being admitted to hospital for what doctors initially believed was a bleeding ulcer.

"The approval of QINLOCK means hope and an opportunity," Mr Turrall said.

"I want to live to see my grandchildren grow. I want to live to be able to experience growing old with my wife. I want to live to be able to spend some time relaxing and enjoying what we have worked for. The approval of QINLOCK will remove a level of anxiety that I live with every day as it provides an opportunity for an additional treatment option."

Mr Turrall said it was critical that PHARMAC now funded QINLOCK for patients to ensure all those who are eligible for treatment can afford the therapy.

"PHARMAC funding will mean the financial burden is eased. We consider ourselves the average Kiwi couple. We have worked hard for what we have accumulated and are looking forward to retirement. We are not sure what we will do if we have to fund (any) treatment ourselves."

QINLOCK belongs to a class of drugs known as tyrosine kinase inhibitors, or TKIs. It is designed to inhibit key enzymes linked to tumour growth. In Australia it has been fully reimbursed on the Pharmaceutical Benefits Scheme since 2021.

A pivotal Phase 3 clinical trial of QINLOCK in patients with advanced GIST – the INVICTUS study – demonstrated that QINLOCK was able to significantly reduce the risk of disease progression by 85% (hazard ratio of 0.15, p<0.0001) with a median progression-free survival (PFS) of 6.3 months in patients administered QINLOCK, compared to 1.0 month in the placebo arm.1 In addition, in a long-term follow up analysis, patients in the QINLOCK arm demonstrated a median overall survival (OS) of 18.2 months compared to 6.3 months in the placebo arm and reduced the risk of death by 59% (hazard ratio of 0.41).1, 4

QINLOCK is made available in New Zealand by independent pharmaceutical company Specialised Therapeutics (ST) under an exclusive distribution agreement from US based Deciphera Pharmaceuticals.

ST Chief Executive Officer Carlo Montagner said QINLOCK was currently under review by PHARMAC.

"We are hopeful for a positive outcome by PHARMAC so that patients with advanced GIST in New Zealand have ready access to this important new treatment option."

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST growth usually begins in the connective tissue in the wall of the affected organ and grows outwards. The common location of GIST is in the stomach (50 to 60%) and small intestines (30 to 40%) but can occur in any site in the digestive system. Other possible GIST sites are the oesophagus, rectum, and colon. The risk of GIST diagnosis increases with age, with GIST incidence peaking among people in their fifties and sixties.5

About QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFRA mutated kinases by using a dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation.6,7 QINLOCK also inhibits primary PDGFRA mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.6,7

On January 19, 2023 10x Genomics (Nasdaq: TXG) reported it will report financial results for the fourth quarter and full year ended December 31, 2022 after market close on Wednesday, February 15, 2023 (Press release, 10x Genomics, JAN 19, 2023, View Source [SID1234626402]). The company’s management will webcast a corresponding conference call beginning at 1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time to discuss its results, business developments and outlook.

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Live audio of the webcast will be available on the "Investors" section of the company website at: www.10xgenomics.com. The webcast will be archived and available for replay for at least 45 days after the event.

On January 19, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), reported the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of MRTX1133, a potential first-in-class oral KRASG12D selective inhibitor for clinical evaluation (Press release, Mirati, JAN 19, 2023, View Source [SID1234626400]). KRASG12D mutations impact approximately 180,000 patients in the US and Europe, representing approximately a 2.5-fold increase in prevalence compared to KRASG12C mutations. No targeted oncology treatment options currently exist for these patients.

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MRTX1133 is a highly potent investigational inhibitor of the KRASG12D driver mutation and demonstrated selective and reversible inhibition of KRASG12D in both its active and inactive states. In addition, MRTX1133 administration resulted in marked tumor response in preclinical KRASG12D mutated pancreatic cancer models as well as lung and colorectal cancer models. MRTX1133 has demonstrated favorable properties including a low risk for off-target activity and drug interactions and a predicted human half-life of greater than 50 hours.

"The clearance by the FDA to initiate clinical evaluation of MRTX1133, the third program in our KRAS franchise to enter clinical development, is illustrative of the innovative approach to drug discovery and demonstrates the best-in-class capabilities of the Mirati team. This particular mutation has been difficult to target, and we are confident in our novel oral formulation strategy, which we believe will enable near-complete target inhibition over the full dosing interval," said James Christensen, Ph.D. chief scientific officer, Mirati Therapeutics, Inc. "We are thrilled to advance MRTX1133 into clinical development and the potential to positively impact people living with KRASG12D-mutated cancers."

The Phase 1/2 clinical trial will launch in early 2023 with plans for multiple expansion cohorts in pancreatic, colorectal, lung and other KRASG12D tumor types.