On October 4, 2021 Oncoinvent AS, a clinical stage company advancing a pipeline of radiopharmaceutical products across a variety of solid cancers, reported that it has appointed Dr. Kari Myren, MD to the role of Chief Medical Officer, Dr. Anne-Kirsti Aksnes to the role of Vice President Clinical Operations, and Mr. Stian Brekke to the role of Head of Regulatory Affairs (Press release, Oncoinvent, OCT 4, 2021, View Source [SID1234590765]).

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Dr. Kari Myren is a medical professional with a strong clinical background with specialty training in surgery. She has ten years of experience from leading positions in both the pharmaceutical and MedTech industries relating to oncology and early phase immuno-oncology, as well as clinical experience from oncologic surgery. Dr. Myren has previously held the positions of Medical Advisor and Senior Medical Advisor at Novartis and Roche Diagnostics respectively. Dr. Myren comes to Oncoinvent from Photocure ASA where she held the position of Vice President Global Medical Affairs and Clinical Development.

Dr. Anne-Kirsti Aksnes is a multi-disciplinary clinical research professional with more than 20 years of experience within clinical research and development in the pharmaceutical and biotech industry. Dr. Aksnes has a strong knowledge of all aspects of clinical development and operations and a broad and reputable experiences with clinical studies in all phases (I-IV). She is a physiologist by training with a Medical Doctorate Degree (PhD) from Karolinska Institute in Sweden. Dr. Aksnes has held multiple senior positions including VP Clinical Development at Targovax ASA and Director of Clinical Research at G.E. Healthcare. Dr. Aksnes also held the position of VP Clinical Development at Algeta ASA and was responsible for the clinical development of Xofigo, a product that has gone on to become the world’s most successful and largest selling radiopharmaceutical.

Mr. Stian Brekke has worked in regulatory affairs since 2005, as a regulatory affairs manager, regulatory project leader and QPPV during 11 years in Pharmaq AS, and since April 2019 as a regulatory affairs director at SMERUD, based in Oslo, Norway. Mr. Brekke has led multiple regulatory submissions to various competent authorities, including marketing authorisation applications, orphan drug designation applications, variation applications, clinical trial applications etc. He has ensured regulatory compliance in close collaboration with clinical R&D units, specialized laboratories, consultants, and regulatory authorities as the regulatory representative in drug development projects.

"I am very pleased that we have been able to attract such qualified and experienced people such as Kari, Anne-Kirsti, and Stian to our team," said Jan A. Alfheim, Chief Executive Officer of Oncoinvent. "I am looking forward to working with them to build Oncoinvent into a world leader in alpha-emitting radiotherapeutics. I would like to use this opportunity to thank Dr. Øyvind Bruland for all his efforts in the development of Radspherin to date, and I look forward to continuing our fine collaboration as he steps into his new role as Senior Medical Advisor and Head of the Radspherin Clinical Advisory Board for Oncoinvent"

Alfheim continued by saying, "I would also like to thank Kari Skinnemoen, our former Head of Regulatory Affairs for all her excellent work and contributions to the development of Radspherin these past four years and I look forward to her continued contributions to the Radspherin development as she begins her transition to retirement."

About Radspherin

Radspherin is a novel alpha-emitting radioactive microsphere suspension designed for treatment of metastatic cancers in body cavities. The radium-224 based therapeutic, Radspherin has shown strong and consistent anticancer activity at doses being essentially non-toxic in preclinical studies. It is anticipated that the product can potentially be used to treat several forms of metastatic cancer.

On October 4, 2021 Bayer reported that Updated thyroid sub-analysis of 29 adult and pediatric TRK fusion cancer patients, of which 28 were evaluable, treated with Vitrakvi (larotrectinib) showed notable overall response rates (ORR) and duration of response (DoR) (Press release, Bayer, OCT 4, 2021, View Source [SID1234590761]). With longer follow-up (data cut-off July 20, 2020) the ORR in 28 evaluable patients was 71% (95% CI 51—87) for all histologies (with 2 [7%] complete responses and 18 [64%] partial responses) and the ORR was 86% (95% CI 64—97) for patients with differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancers. Among 7 patients with anaplastic thyroid cancer (ATC), the ORR was 29% (95% CI 4—71).1 These data were presented in an oral presentation on October 2, 2021 from 12:00 – 1:00 PM EST at the virtual American Thyroid Association 2021 Annual Meeting.

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Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Patients should be selected for therapy based on a Food and Drug Administration (FDA)-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.2

"Being one of the more common solid tumors, thyroid cancer – specifically papillary thyroid cancer – has one of the highest NTRK fusion prevalence rates of up to 25%,3 especially in younger patients," said Steven G. Waguespack, M.D., Professor of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center. "In patients with thyroid cancer who harbor an NTRK gene fusion and who require systemic therapy for advanced disease, these data support larotrectinib’s potential as an appropriate treatment option."

Among all patients with thyroid cancer, overall median time to response was 1.9 months (range 1.6—3.7). Kaplan-Meier estimated 24-month rate for DoR was 81% (95% CI 60—100). Two patients (7%) had Grade 3 TRAEs and no patients discontinued treatment due to adverse events. This analysis pooled data from three Vitrakvi clinical trials (NCT02122913, NCT02576431 and NCT02637687) in adult and pediatric patients with TRK fusion cancer.1

"With three years of follow-up and an expanded patient population, these results provide additional evidence to support Vitrakvi’s use in NTRK gene fusion-positive thyroid cancer," said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. "These data in patients with thyroid cancer further underscore the importance of integrating biomarker-driven oncology medicines into cancer care, so that appropriate patients can potentially benefit from a targeted treatment approach."

About Vitrakvi (larotrectinib)

Vitrakvi (larotrectinib) is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

Select patients for therapy based on an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information for Vitrakvi (larotrectinib)

Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances.

In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients.

Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption.

Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients.

Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption.

Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption.

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients.

Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures.

Hepatotoxicity: In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) patients.

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. VITRAKVI resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%).

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

Please see the full Prescribing Information for VITRAKVI (larotrectinib).

About TRK Fusion Cancer

TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing a chimeric TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins are oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon and rectal, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (including secretory carcinoma of the salivary gland) and pediatric cancers (infantile fibrosarcoma and other soft tissue sarcomas).2,5

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On October 4, 2021 Ambrx (NYSE: AMAM), a clinical stage biopharmaceutical company using an expanded genetic code technology platform to create Engineered Precision Biologics, reported that NovoCodex Pharmaceuticals Ltd. (NovoCodex), Ambrx’s partner in China, presented positive interim data from the ACE-Gastric-01 Phase 1 clinical study of ARX788 for the treatment of HER2+ metastatic gastric / gastroesophageal junction (GEJ) cancer at The Chinese Society of Clinical Oncology (CSCO) (Press release, Ambrx, OCT 4, 2021, View Source [SID1234590760]). The newly presented data suggests that ARX788 at a 1.7 mg/kg dose has a tolerable safety profile. The data presented here adds to and updates trial data that Ambrx presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2021. Ambrx received Orphan Drug designation from the FDA for the treatment of gastric cancer, including cancer at the GEJ, in early 2021.

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Updated ACE-Gastric-01 Phase 1 Interim Data Highlights

(Data as of June 30, 2021)

7 patients dosed at 1.7 mg/kg every three weeks.
Demonstrated overall response rate (ORR) of 44.4% (12/27) in the response-evaluable patients across all three cohorts (1.3 mg/kg, 1.5 mg/kg, 1.7 mg/kg every three weeks).
Low drug-related severe adverse events (SAE) occurred in 6.7% (2/30) of all treated patients across all three cohorts (1.3 mg/kg, 1.5 mg/kg, 1.7 mg/kg every three weeks). Drug-related grade 3 and above adverse events (AEs) comprised only 10% (3/30).
As expected, the most common AEs observed were ocular-related and dose-dependent.
Median overall survival (mOS) of 10.7 months across all three cohorts (1.3 mg/kg, 1.5 mg/kg, 1.7 mg/kg every three weeks) and mOS for the 1.7 mg/kg cohort has not been reached.
Enrollment in ACE-Gastric-01 is completed with ongoing follow-up.

Source: NovoCodex, CSCO 2021 presentation.

"We are thrilled with the progress from the NovoCodex sponsored study of our lead clinical asset, ARX788, and look forward to continuing our collaboration as we explore the capabilities of our antibody drug conjugate in treating HER2 positive cancers and solid tumors," said Feng Tian, Ph.D., Chairman of the Board, President and CEO of Ambrx. "We are encouraged by the continued positive data from the ACE-Gastric-01 study and we look forward to enrolling more patients in our ongoing global co-sponsored ACE-Gastric-02 Phase 2/3 trial."

ACE-Gastric-01 is a Phase 1 clinical study of ARX788 for the treatment of HER2+ metastatic gastric/GEJ cancer that is being conducted in China by Ambrx’s partner, NovoCodex. The ongoing clinical study recently completed enrollment of 30 patients and is designed to be a dose escalation and expansion study with patients receiving treatment doses of 1.3 mg/kg, 1.5 mg/kg, or 1.7 mg/kg every 3 weeks. Ambrx previously presented data from two Phase 1 studies of ARX788 at ASCO (Free ASCO Whitepaper) where patients received a dose of ARX788 up to 1.5 mg/kg every three weeks or every four weeks.

In August 2021, NovoCodex also announced the dosing of the first patient in the Ambrx and NovoCodex co-sponsored global Phase 2/3 trial of ARX788 in HER2+ gastric cancer. ACE-Gastric-02 is a multicenter, randomized, controlled clinical trial to evaluate the efficacy and safety of ARX788 in patients with HER2+ advanced gastric or gastroesophageal junction adenocarcinoma.

On October 4, 2021 Novocure (NASDAQ: NVCR), a global oncology company working to extend survival in some of the most aggressive forms of cancer, and Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688), an innovative commercial-stage biopharmaceutical company, reported that the final patient has been enrolled in a Novocure-sponsored phase 2 pilot trial conducted by Zai Lab evaluating the safety and efficacy of Tumor Treating Fields (TTFields) in combination with chemotherapy as a first-line treatment in patients with gastric adenocarcinoma (Press release, NovoCure, OCT 4, 2021, View Source [SID1234590758]). Final data collection is expected in the first half of 2022.

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"The execution of this phase 2 pilot trial in gastric cancer reflects our commitment to bringing Tumor Treating Fields to as many patients as possible in Greater China," said Alan Sandler, M.D., President and Head of Global Development, Oncology at Zai Lab. "Gastric cancer is the third most common cancer in China in incidence and mortality and a significant unmet medical need. Late diagnosis contributes to poor prognosis in advanced gastric cancer patients. This trial, conducted entirely in China, showcases Zai’s capabilities as we partner with Novocure to expand treatment options for gastric cancer patients in China."

The phase 2 pilot gastric cancer trial of TTFields has enrolled approximately 30 patients in Greater China. The single arm, open-label, multi-center study is investigating the safety and efficacy of TTFields in combination with chemotherapy as the first-line treatment of unresectable gastric adenocarcinoma, or gastroesophageal junction adenocarcinoma. In the study, patients receive TTFields and XELOX (capecitabine / oxaliplatin) chemotherapy until disease progression. The primary endpoint is investigator-assessed objective response rate. The protocol is designed to include 25 evaluable patients who receive at least one tumor assessment.

"We believe that Tumor Treating Fields’ mechanism of action is broadly applicable to treat solid tumor cancers," said Asaf Danziger, Novocure’s Chief Executive Officer. "We look forward to seeing results from this phase 2 pilot trial with our partner, Zai Lab, and to further exploring the potential of Tumor Treating Fields as a treatment for gastric cancer."

About Gastric Cancer

Gastric cancer is the third largest cancer in China. According to Globocan 2020 estimates, more than one million new gastric cancer cases are diagnosed worldwide annually, and approximately half of all gastric cancer cases occur in China. Currently, the five-year survival rate of locally advanced or metastatic gastric cancer ranges from 5 percent to 20 percent, and the median overall survival is approximately one year.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields are intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 20,000 patients have been treated with TTFields.

On October 4, 2021 Novocure (NASDAQ: NVCR) reported that it will report financial results for the third quarter 2021 on Thursday, October 28, 2021, before the U.S. financial markets open (Press release, NovoCure, OCT 4, 2021, View Source [SID1234590756]). Novocure’s management will host a conference call and webcast to discuss its financial results for the three and nine months ended September 30, 2021, at 8 a.m. EDT on Thursday, October 28, 2021. Analysts and investors can participate in the conference call by dialing 855-442-6895 for domestic callers and 509-960-9037 for international callers, using the conference ID 6394785.

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The webcast, earnings slides presented during the webcast and the corporate presentation can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for at least 14 days following the call. Novocure has used, and intends to continue to use, its investor relations website, as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.