On April 23, 2020 GlaxoSmithKline plc (LSE/NYSE:GSK) reported data from an updated analysis of the GARNET trial, which demonstrated that dostarlimab, an investigational anti-programmed death-1 (PD-1) monoclonal antibody, provided clinically meaningful results in women with recurrent or advanced mismatch repair-deficient (dMMR) endometrial cancer who progressed on or after a platinum-based regimen (Press release, GlaxoSmithKline, APR 23, 2020, View Source [SID1234556555]).

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This updated analysis included patients with dMMR endometrial cancer who had measurable disease at baseline and ≥6 months of follow-up by the data cutoff (n=71). Patients received 500 mg of dostarlimab once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression. The primary endpoints were confirmed objective response rate (ORR) and duration of response (DOR), as assessed against RECIST v 1.1 by blinded independent central review. GARNET is the largest dataset evaluating an anti-PD-1 in endometrial cancer.

Treatment with dostarlimab showed an ORR of 42% (95% CI; 31-55) and a disease control rate of 58% (95% CI; 45-69). Overall, 13% of patients had a complete response and 30% of patients had a partial response. At the time of data cutoff, with a median follow up of 11.2 months, the median DOR had not been reached (1.87+ to 19.61+ months).

Dr. Axel Hoos, Senior Vice President and Head Oncology R&D, GSK said: "We are committed to developing medicines for patients who face high unmet medical need. We believe in the clinical potential of dostarlimab for women with advanced or recurrent dMMR endometrial cancer who urgently need additional treatment options for this incurable disease."

Dr. Ana Oaknin, Head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, and primary investigator for GARNET said: "There are limited treatment options for women with advanced or recurrent endometrial cancer, and prognosis of these patients is poor. The results observed in the GARNET trial indicate the potential of dostarlimab to offer a new treatment option for women with this challenging disease."

The safety population included all patients with dMMR endometrial cancer who received at least one dose of dostarlimab (n=104). Results showed that dostarlimab was well tolerated with a low discontinuation rate (2%) due to treatment-related adverse events (TRAEs), consistent with the safety profiles of other anti-PD-1 therapies. The most commonly reported TRAEs were asthenia (15%), diarrhea (15%), fatigue (14%), and nausea (13%). No deaths associated with dostarlimab were reported in the study.

Dostarlimab is not currently approved for use anywhere in the world.

About GARNET
The ongoing phase I GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumors. Part 2B of the study includes five expansion cohorts: dMMR/microsatellite instability-high (MSI-H) endometrial cancer (cohort A1), mismatch repair-proficient endometrial cancer (cohort A2), non-small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial cancer (cohort F), and platinum-resistant ovarian cancer without BRCA mutations (cohort G). GARNET is still enrolling patients.i,ii

About Dostarlimab
Dostarlimab is an investigational humanized anti-PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.iii

In addition to GARNET, dostarlimab is being investigated for women with recurrent or primary advanced endometrial cancer in combination with standard of care (chemotherapy) in the phase III RUBY trial.iv Dostarlimab is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumors or metastatic cancer.

About Endometrial Cancerv
Endometrial cancer is a main type of uterine cancer that forms in the inner lining of the uterus, known as the endometrium. Endometrial cancer can be classified as mismatch repair-deficient/microsatellite instability-high or mismatch repair-proficient/microsatellite stable. There are limited treatment options for women whose disease progresses on or after first-line therapy. Endometrial cancer is the sixth most common cancer in women worldwide.vi

GSK in Oncology
GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilizing modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On April 23, 2020 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that it will host a conference call at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, May 7, 2020, following the release of its first quarter 2020 financial results (Press release, Puma Biotechnology, APR 23, 2020, View Source [SID1234556554]).

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The call may be accessed by dialing 1-866-548-4713 (domestic) or 1-323-794-2093 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 90 days.

On April 23, 2020 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported it will release its first quarter 2020 financial results after the market closes on Thursday, May 7, 2020 (Press release, Personalis, APR 23, 2020, View Source [SID1234556553]). In conjunction with the release, the Company will host a conference call and webcast that day at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss its financial results and recent highlights.

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Interested parties may access the live call via telephone by dialing (866) 220-8061 for domestic callers or (470) 495-9168 for international callers, using conference ID: 9370329. The live webinar of the call may be accessed by visiting the Events section of the company’s website at investors.personalis.com. A replay of the webinar will be available shortly after the conclusion of the call and will be archived on the company’s website.

On April 23, 2020 CEL-SCI Corporation (NYSE American: CVM) reported that the Independent Data Monitoring Committee (IDMC) for the Company’s pivotal Phase 3 head and neck cancer study of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) has completed its recent review of the Phase 3 study data (Press release, Cel-Sci, APR 23, 2020, View Source [SID1234556552]). The IDMC meets periodically to review the safety and efficacy of the ongoing Phase 3 study. The data from all 928 enrolled patients were provided to the IDMC by the clinical research organization (CRO) responsible for data management of this Phase 3 study.

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The IDMC made the following recommendation:

The IDMC "agrees with continuing the trial without change".
IDMCs are committees commonly used by sponsors of clinical trials to protect the interests of the patients and the integrity of the study data in ongoing trials, especially when the trials involve patients with life threatening diseases, and when, as in cancer clinical trials, they extend over long periods of time.

On April 23, 2020 Bayer reported additional clinical trial results for Vitrakvi (larotrectinib) and latest research on its investigational small molecule aryl hydrocarbon receptor (AhR) inhibitor BAY 2416964 to be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting I from April 27-28, 2020 (Press release, Bayer, APR 23, 2020, View Source [SID1234556551]). Data at this meeting underscore Bayer’s continued efforts to explore the potential of clinical stage projects in oncology from the laboratory to clinical practice and share the latest study progress with the scientific community. The original AACR (Free AACR Whitepaper) program will be presented in segments in two AACR (Free AACR Whitepaper) Virtual Annual Meetings, with the first part taking place from April 27-28. Access to AACR (Free AACR Whitepaper) Virtual Annual Meeting I will be made freely available. More details can be found here. The abstracts of these proffered paper presentations will be posted online at 12:01 a.m. EDT on Monday, April 27.

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"We are committed to making our potentially practice-changing research on treatment approaches available to doctors and to people living with cancer," said Scott Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. "Bayer’s approach to cancer research includes investing in drug development and testing programs designed to help ensure that the right patients get the right treatment. At AACR (Free AACR Whitepaper), we will share important clinical trial analyses that help inform the selection of patients who may be eligible for our TRK inhibitor Vitrakvi. In addition, Bayer will also share research on a potential new approach in immuno-oncology."

Two analyses from the Vitrakvi clinical trials will be shared. The first analysis includes a Plenary Session presentation on Vitrakvi efficacy and safety data based on the presence of neurotrophic receptor tyrosine kinase (NTRK) gene fusions or other alterations, and the second includes data on outcomes in patients with TRK fusion cancer by prior therapy and performance status. Vitrakvi is approved in the U.S., Canada, Brazil and the European Union (EU). In the U.S., Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have an 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Additional filings in other regions are underway or planned.

At the virtual meeting, for the first time, the structure and functional characterization of the investigational small molecule AhR inhibitor BAY 2416964 will be presented. The AhR receptor is expressed in many different immune cells and is considered to play an important role in immuno-suppression within the tumor microenvironment. An AhR inhibitor such as BAY 2416964 is thought to reactivate anti-tumor immune responses in a manner distinct from currently approved checkpoint inhibitors, and thus may provide a new approach for cancer immunotherapy. BAY 2416964 is currently investigated in a first-in-human, Phase I trial in patients with advanced solid malignancies. Immuno-oncology (IO) is a key area of research for Bayer.

Presentations for the Virtual Annual Meeting I are listed below:

Presentations:

Efficacy and safety of larotrectinib in patients with cancer and NTRK gene fusions or other alterations
Virtual Plenary Session: VCTPL06 – Targeted Therapy
Abstract: 10363
April 28, 4:20 – 4:30 pm (EDT)
Larotrectinib in TRK fusion cancer patients: outcomes by prior therapy and performance status
Virtual Poster Session: VPO.CT02 – Phase II Clinical Trials
Abstract: CT199
April 27, 9:00 am – 6:00 pm (EDT)
BAY 2416964: The first Aryl Hydrocarbon Receptor (AhR) inhibitor to enter phase I clinical development as a novel cancer immunotherapy
Virtual Symposium: VSY.DDT01 – New Drugs on the Horizon: Part 1
Abstract: DDT01-02
April 27, 5:17 – 5:37 pm (EDT)
About Vitrakvi (larotrectinib)1

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

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)

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurologic adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).

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 dose when resumed.

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of 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. Larotrectinib 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%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).

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 Bayer’s Oncology Research Platforms

Bayer focuses its research activities on first-in-class innovations across the following scientific platforms: Oncogenic Signaling, Targeted Alpha Therapies, and Immuno-Oncology. In the field of Oncogenic Signaling the company is developing small molecules and other modalities to target crucial pathways of intracellular tumor signaling that are responsible for the development and survival of cancer in well-defined patient populations identified using selection biomarker. In regard to Targeted Alpha Therapies drug candidates are being developed using the company’s proprietary Thorium-227 platform for delivering high-energy alpha-radiation via different targeting molecules such as antibodies to tumor cells. In Immuno-Oncology Bayer is developing next-generation treatments that intervene at different levels of the cancer immunity cycle specifically addressing patients not responding to immune checkpoint inhibitors.

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 now expands to 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.