On October 30, 2023 GSK plc (LSE/NYSE: GSK) reported positive headline results from a planned analysis of Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial investigating Jemperli (dostarlimab) plus standard-of-care chemotherapy (carboplatin and paclitaxel), followed by dostarlimab as a single agent, compared to placebo plus chemotherapy followed by placebo in adult patients with primary advanced or recurrent endometrial cancer (Press release, GlaxoSmithKline, OCT 30, 2023, View Source [SID1234636442]). The trial met its primary endpoint of overall survival (OS), demonstrating a statistically significant and clinically meaningful benefit in the overall patient population.

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A clinically meaningful OS benefit was observed in both prespecified subpopulations in the trial: mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and mismatch repair proficient (MMRp)/microsatellite stable (MSS) patient subgroups. OS is one of two primary endpoints in the RUBY Part 1 trial. Previously, the trial met its other primary endpoint of progression-free survival (PFS), demonstrating a 72% and 36% reduction in the risk of disease progression or death observed in the dMMR/MSI-H population (HR: 0.28 [95% CI: 0.16-0.50]) and overall patient population (HR: 0.64 [95% CI: 0.51–0.80]), respectively1.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "With today’s headline results from Part 1 of the phase III RUBY trial, dostarlimab plus chemotherapy has become the only immuno-therapy combination to show a survival benefit in this broader patient population in this treatment setting. We look forward to sharing detailed results of this analysis with regulatory authorities and the larger scientific community."

Full results from this latest analysis from the trial will be published in a medical journal and presented at an upcoming scientific meeting.

The safety and tolerability profile of dostarlimab plus carboplatin and paclitaxel was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 25%) in patients receiving dostarlimab plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, diarrhoea and myalgia.

Currently, Jemperli has regulatory approvals in a certain subset of patients with endometrial cancer based on the previously reported positive results for the primary endpoint of progression-free survival in Part 1 of the RUBY trial. In July 2023, Jemperli received FDA approval in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). Jemperli was also approved in the United Kingdom in October 2023 in combination with platinum-containing chemotherapy for the treatment of adult patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy. The application remains under review in the European Union (EU), Australia, Canada, Switzerland and Singapore.

About endometrial cancer

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries, with approximately 417,000 new cases reported each year worldwide2, and incidence rates are expected to rise by almost 40% between 2020 and 2040.3,4 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5

About RUBY
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

The dual-primary endpoints in Part 1 are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the dMMR/MSI-H and ITT populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma. In Part 2, the primary endpoint is investigator-assessed PFS. Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

About Jemperli (dostarlimab)
Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.6

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H), and as a single agent for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. The sBLA supporting the indication in combination with carboplatin and paclitaxel received Breakthrough Therapy designation from the FDA. Jemperli is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: Jemperli (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these medicines under the agreement.

Important Information for Jemperli in the EU

Indication 

Jemperli is indicated as monotherapy for treating adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

Refer to the Jemperli EMA Reference Information for a full list of adverse events and the complete important safety information in the EU.

On October 30, 2023 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for solid and liquid malignancies and inflammatory diseases based on its unique Mimicry platform, reported that it received a €3 million investment from The Leukemia & Lymphoma Society’s Therapy Acceleration Program (LLS TAP) (Press release, Enterome, OCT 30, 2023, View Source [SID1234636441]). The funding will propel the Company’s ongoing Phase 2 SIDNEY study of EO2463 in indolent non-Hodgkin B-cell lymphoma (iNHL).

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"We are excited to support the clinical development of Enterome’s innovative OncoMimics platform to the benefit of blood cancer patients," said Lore Gruenbaum, Ph.D., Vice President, LLS TAP. "The observed good safety profile of EO2463 together with its unique mechanism of immune activation may create a substantial benefit for blood cancer patients and open the door to treatment at earlier stages of disease. Moreover, it could provide a key building block for the next generation of combination and maintenance therapies."

"We are honored to be recognized and supported by LLS’s Therapy Acceleration Program," said Dr. Pierre Belichard, Chief Executive Officer of Enterome. "This investment represents a significant vote of confidence in our OncoMimics-based immunotherapies. It also provides us with immediate capital and access to guidance from the most renowned scientists and experts in the field of liquid tumors, facilitating the acceleration of our ongoing Phase 2 SIDNEY study of EO2463 in iNHL. With LLS’s support, we are poised to bring this potentially transformative therapy to patients battling iNHL."

"EO2463 was designed to mimic certain proteins on B lymphocytes, activate pre-existing memory T cells, and drive anti-tumor activity against B-cell malignancies," said Dr. Jan Fagerberg, Chief Medical Officer of Enterome. "This unique, OncoMimics-based approach specifically targets and reduces malignant B cells in iNHL. Initial results have shown promising efficacy and tolerability in iNHL B-cell lymphomas. We look forward to our collaboration with LLS and to the continued advancement of our clinical program."

SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with indolent non-Hodgkin lymphoma (iNHL). The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in approximately 60 patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL). For more information on the study, refer to Clinicaltrials.gov identifier: NCT04669171.

About EO2463

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37 and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2).

About OncoMimics

OncoMimics immunotherapies are designed to activate pre-existing effector memory T cells that target bacterial (non-self) peptides, which are strongly cross-reactive against selected Tumor-Associated Antigens (TAAs), or B cell markers expressed on tumoral cells, resulting in a rapid, targeted cytotoxic response against cancer.

On October 30, 2023 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported financial results for the third quarter ended September 30, 2023 and provided a corporate update (Press release, Deciphera Pharmaceuticals, OCT 30, 2023, View Source [SID1234636440]).

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"QINLOCK achieved another record quarter of product revenue with continued strength in commercial demand," said Steve Hoerter, President and Chief Executive Officer of Deciphera Pharmaceuticals. "With the positive results of the MOTION Phase 3 study of vimseltinib we reported earlier today, we are now one step closer to becoming a company with multiple approved products. We look forward to engaging with regulatory authorities to advance vimseltinib toward approval and deliver it to the TGCT patients in need of an effective and well tolerated treatment option."

Third Quarter 2023 Highlights and Upcoming Milestones

QINLOCK (ripretinib)

Recorded $41.8 million in QINLOCK net product revenue in the third quarter of 2023, including $32.7 million in U.S. net product revenue and $9.1 million in international net product revenue, an increase of 29% compared to net product revenue of $32.3 million in the third quarter of 2022. In addition, QINLOCK generated $1.5 million in collaboration revenue including royalties and supply revenue with Zai Lab, the Company’s partner in Greater China.
Successfully launched QINLOCK in Italy for the treatment of fourth-line gastrointestinal stromal tumor (GIST).
Initiated the INSIGHT Phase 3 study by opening the first sites for enrollment comparing QINLOCK versus sunitinib in second-line GIST patients with mutations in KIT exon 11 and 17/18.
Vimseltinib

Announced positive top-line results from the MOTION pivotal Phase 3 study of vimseltinib, an investigational, orally administered, potent, and highly selective switch-control kinase inhibitor of CSF1R for the potential treatment of tenosynovial giant cell tumor (TGCT). The study met its primary endpoint in the intent-to-treat (ITT) population demonstrating statistically significant and clinically meaningful improvements in objective response rate (ORR) at Week 25 compared to placebo. In the ITT population, the ORR at Week 25 was 40% for the vimseltinib arm and 0% for the placebo arm (p-value <0.0001). In addition, the study met all key secondary endpoints demonstrating statistically significant and clinically meaningful improvements in tumor volume score (TVS), range of motion (ROM), physical function, stiffness, quality of life, and pain compared to placebo. In the ITT population, the ORR by TVS at Week 25 was 67% for the vimseltinib arm and 0% for the placebo arm (p<0.0001). Treatment with vimseltinib also demonstrated an improvement in ROM at Week 25 of 18.4% vs. a 3.8% improvement for placebo (p=0.0077). Treatment with vimseltinib was well-tolerated in patients with TGCT and the safety profile was consistent with previously disclosed data. There was no evidence of cholestatic hepatotoxicity.
Announced updated results from the Phase 1/2 study of vimseltinib as of a June 27, 2023 cutoff date demonstrating strong clinical benefit with best overall response rates of 72% (Phase 1) and 64% (Phase 2 Cohort A), a favorable long-term safety profile with no evidence of cholestatic hepatotoxicity and increasing median treatment duration of 25.1 months (Phase 1) and 21.0 months (Phase 2 Cohort A). Results from the Phase 1 portion of the study are being presented in an oral presentation and results from Cohorts A and B of the Phase 2 portion of the study are being presented in two poster presentations at the Connective Tissue Oncology Society 2023 Annual Meeting in Dublin, Ireland on November 1-4, 2023.
Expects to submit a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in the second quarter of 2024 and a Marketing Authorisation Application (MAA) with the European Medicines Agency (EMA) in the third quarter of 2024.
DCC-3116

Enrollment is ongoing in combination escalation cohorts evaluating the potential first-in-class ULK inhibitor, DCC-3116, in combination with binimetinib, trametinib, sotorasib, encorafenib/cetuximab, and QINLOCK, designed to select recommended Phase 2 combination dosing for potential expansion cohorts.
DCC-3084

Expects to submit an Investigational New Drug (IND) application to the FDA for its pan-RAF inhibitor, DCC-3084, by year end 2023.
DCC-3009

Expects to submit an IND application to the FDA for its pan-KIT inhibitor, DCC-3009, in the first half of 2024.
Third Quarter 2023 Financial Results

Revenue: Total revenue for the third quarter of 2023 was $43.3 million, which includes $41.8 million of net product revenue of QINLOCK and $1.5 million of collaboration revenue compared to $36.0 million of total revenue, including $32.3 million of net product revenue of QINLOCK and $3.7 million of collaboration revenue, for the same period in 2022.
Cost of Sales: Cost of sales were $1.3 million in the third quarter of 2023 compared to cost of sales of $3.3 million for the third quarter of 2022. In the third quarter of 2022, Deciphera completed the sale of zero cost inventories of QINLOCK that had been expensed prior to FDA approval.
R&D Expenses: Research and development expenses for the third quarter of 2023 were $62.5 million, compared to $47.5 million for the same period in 2022. The increase was primarily due to an increase in clinical study costs for QINLOCK and clinical study costs related to the Phase 1/2 study of DCC-3116. Non-cash, stock-based compensation was $5.0 million and $5.3 million for the third quarters of 2023 and 2022, respectively.
SG&A Expenses: Selling, general, and administrative expenses for the third quarter of 2023 were $33.3 million, compared to $30.0 million for the same period in 2022. The increase was primarily due to an increase in professional, consulting, and other expenses as well as personnel-related costs. Non-cash, stock-based compensation was $6.1 million and $7.1 million for the third quarters of 2023 and 2022, respectively.
Net Loss: For the third quarter of 2023, Deciphera reported a net loss of $49.6 million, or $0.58 per share, compared with a net loss of $43.0 million, or $0.55 per share, for the same period in 2022.
Cash Position: As of September 30, 2023, cash, cash equivalents, and marketable securities were $376.9 million, compared to $389.4 million as of June 30, 2023. Based on its current operating plans, Deciphera expects its current cash, cash equivalents, and marketable securities together with anticipated product, royalty, and supply revenues, but excluding any potential future milestones received under its collaboration or license agreements, will enable the Company to fund its operating and capital expenditures into 2026.
Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss this announcement today, October 30, 2023, at 8:00 AM ET. The conference call may be accessed via this link: https://register.vevent.com/register/BIc2885b197da74145bfc30deb5fb11858. A live webcast of the conference call will be available in the "Events and Presentations" page in the "Investors & News" section of the Company’s website at View Source A replay will be available on the Company’s website approximately two hours after the conference call and will be available for 30 days following the call.

On October 30, 2023 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported positive top-line results from the MOTION pivotal Phase 3 study of vimseltinib in patients with TGCT not amenable to surgery (Press release, Deciphera Pharmaceuticals, OCT 30, 2023, View Source [SID1234636439]). Vimseltinib is the Company’s investigational, orally administered, potent, and highly selective switch-control kinase inhibitor of CSF1R.

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"Patients suffering from TGCT are in need of a new treatment option that offers both strong clinical benefit and a well-tolerated safety profile," said Hans Gelderblom, M.D., Ph.D., Chair of the Department of Medical Oncology at Leiden University Medical Center. "TGCT has a significant negative impact on the daily life of patients who face substantial pain, stiffness, and impaired mobility. Success across both the primary and all key secondary endpoints in MOTION underscores vimseltinib’s ability to help TGCT patients feel and function better. The top-line results from MOTION, together with the impressive data announced today from the Phase 1/2 study showing that the response rates with vimseltinib continue to increase over time, and that patients continue to receive long-term clinical benefit as evidenced by the median duration of treatment, demonstrates vimseltinib’s potential to become a best-in-class agent."

"We are excited about the potential for vimseltinib to become our next approved medicine, supporting our continued evolution to a company with multiple marketed products," said Steve Hoerter, President and Chief Executive Officer of Deciphera Pharmaceuticals. "The totality of data shown today demonstrate the potential for vimseltinib to offer a new and differentiated treatment option for patients with TGCT. On behalf of the entire Deciphera team, I would like to thank the patients, their caregivers, and the healthcare professionals who participated in the MOTION and Phase 1/2 studies. We look forward to working with regulatory agencies worldwide as we focus on delivering this important new treatment option to patients with TGCT."

Top-line Results from the MOTION Pivotal Phase 3 Study of Vimseltinib in TGCT

The MOTION pivotal Phase 3 study is a two-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed). In Part 1, patients (n=123) were randomized two-to-one to receive either 30 mg twice weekly of vimseltinib (n=83) or placebo (n=40) for 24 weeks. The primary endpoint of the study is ORR at Week 25 as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent radiologic review (IRR). The open-label Part 2 portion of MOTION, in which patients from both the vimseltinib and placebo arms receive treatment with vimseltinib, remains ongoing. The results for Part 1 of the study are based on a data cutoff date of August 22, 2023.

The study met its primary endpoint in the intent-to-treat (ITT) population demonstrating statistically significant and clinically meaningful improvement versus placebo in ORR at Week 25 based on IRR per RECIST v1.1. In the ITT population, the ORR at Week 25 was 40% (95% CI: 29%, 51%) for the vimseltinib arm and 0% (95% CI: 0%, 9%) for the placebo arm resulting in a response difference (vimseltinib versus placebo) of 40% (95% CI: 29%, 51%) (p<0.0001).

In addition to meeting the primary endpoint, the study also achieved statistically significant and clinically meaningful improvements versus placebo in all key secondary endpoints assessed at Week 25 including ORR per tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain.

In the ITT population, the ORR at Week 25 based on IRR per TVS was 67% (95% CI: 56%, 77%) for the vimseltinib arm and 0% (95% CI: 0%, 9%) for the placebo arm (p<0.0001). Treatment with vimseltinib also demonstrated an improvement in mean change from baseline in active ROM at Week 25 of 18.4% versus a 3.8% improvement for placebo (p=0.0077).

Vimseltinib was well-tolerated and the safety profile in the MOTION study was consistent with previously disclosed data. There was no evidence of cholestatic hepatotoxicity in patients treated with vimseltinib. Patients with treatment-emergent adverse events (TEAEs) leading to treatment discontinuation was 6% in the vimseltinib arm. The table below lists TEAEs >15% in either arm during Part 1 of the study.

Preferred Term n (%)

Vimseltinib
(n=83)

Placebo
(n=39)1

All Grades

Grade 3/4

All Grades

Grade 3/4

Periorbital edema^

37 (45%)

3 (4%)

5 (13%)

0

Fatigue ^

27 (33%)

0

6 (15%)

0

Face edema^

26 (31%)

1 (1%)

3 (8%)

0

Pruritus^

24 (29%)

2 (2%)

3 (8%)

0

Headache^

23 (28%)

1 (1%)

10 (26%)

0

Asthenia^

22 (27%)

1 (1%)

9 (23%)

1 (3%)

Nausea ^

21 (25%)

0

8 (21%)

1 (3%)

CPK increased

20 (24%)

8 (10%)

0

0

AST increased

19 (23%)

0

1 (3%)

0

Arthralgia ^

16 (19%)

0

6 (15%)

1 (3%)

Rash ^

16 (19%)

0

2 (5%)

0

Rash maculo-papular^

16 (19%)

1 (1%)

0

0

Edema peripheral ^

15 (18%)

0

3 (8%)

0

Hypertension

14 (17%)

4 (5%)

4 (10%)

1 (3%)

Diarrhea

10 (12%)

0

8 (21%)

1 (3%)

(1) Does not include one patient randomized to placebo that did not receive study drug.

TEAE incidence is based on maximum grades per CTCAE v5.0. The only Grade 4 adverse events were CPK Increased observed in two patients. TEAEs leading to dose interruption were 44 (53%) and dose reduction 35 (42%). ^ Denotes adverse events without Grade 4 criteria per CTCAE v5.0.

The Company expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for vimseltinib for the treatment of patients with TGCT in the second quarter of 2024 and a Marketing Authorisation Application (MAA) to the European Medicines Agency in the third quarter of 2024.

Additional efficacy and safety results from Part 1 of the MOTION study are expected to be presented at an upcoming medical meeting.

Updated Results from the Phase 1/2 Study of Vimseltinib in TGCT

The Company also announced today updated results from the Phase 1/2 open-label, multicenter study evaluating the safety and efficacy of vimseltinib in patients with TGCT, which will be presented at the Connective Tissue Oncology Society 2023 Annual Meeting in Dublin, Ireland on November 1-4, 2023.

As of the June 27, 2023 cutoff date, 97 patients were enrolled in the study as follows:

Phase 1: 32 patients enrolled in three cohorts across multiple doses.
Phase 2: 65 patients enrolled in two cohorts at the recommended Phase 2 dose of 30 mg twice weekly: Cohort A (n=46) in TGCT patients with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed); and Cohort B (n=19) in TGCT patients with prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib alone not eligible).
Antitumor Activity and Treatment Duration:

93 patients were evaluable for efficacy by RECIST v1.1 at the data cutoff date; response data is based on IRR summarized as follows:

Phase 1

(n=32)

Phase 2 Cohort A

(n=45)

Phase 2 Cohort B

(n=16)

Best ORR per RECIST v1.1 by IRR (%)

72%

64%

(38% at Week 25)

44%

Median Duration of Response

(months) (Range)

NR (3.8+, 45.2+)

NR (0.03+, 25.4+)

NR (4.0+, 21.0+)

Median Treatment Duration

(months) (Range)

25.1 (0.7, 46.9)

21.0 (0.2, 30.3)

7.3 (0.7, 27.4)

Patients Active on Treatment at Cutoff Date (%)

47%

48%

74%

NR: Not Reached by Kaplan-Meier analysis.

In addition, updated data from Cohorts A and B of the Phase 2 study demonstrate that patients experienced clinically meaningful symptomatic benefit at Week 25 across multiple secondary efficacy measures including best ORR per TVS (Cohort A), active range of motion, physical function, stiffness, and pain.

Safety and Tolerability

Treatment with vimseltinib was well-tolerated in patients with TGCT and consistent with previously disclosed data.
There was no evidence of cholestatic hepatotoxicity.
Treatment discontinuation due to TEAEs occurred in 9% of patients.
Results from the Phase 1 portion of the study are being presented in an oral presentation, titled "Safety and Efficacy Updates from a Phase 1 Study of Vimseltinib in Patients with Tenosynovial Giant Cell Tumor." Results from Cohorts A and B of the Phase 2 portion of the study are being presented in two poster presentations, titled "Safety, Efficacy, and Patient-Reported Outcomes with Vimseltinib in Patients with Tenosynovial Giant Cell Tumor Who Received No Prior Anti-Colony-Stimulating Factor 1 Therapy: Ongoing Phase 2 Update" and "Safety, Efficacy, and Patient-Reported Outcomes with Vimseltinib in Patients with Tenosynovial Giant Cell Tumor Who Received Prior Anti-Colony-Stimulating Factor 1 Therapy: Ongoing Phase 2 Update." The presentations are available on the Company’s website at www.deciphera.com/presentations-publications.

Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss this announcement today, October 30, 2023, at 8:00 AM ET. The conference call may be accessed via this link: https://register.vevent.com/register/BIc2885b197da74145bfc30deb5fb11858. A live webcast of the conference call will be available in the "Events and Presentations" page in the "Investors & News" section of the Company’s website at View Source A replay will be available on the Company’s website approximately two hours after the conference call and will be available for 30 days following the call.

On October 30, 2023 Day One Biopharmaceuticals (Nasdaq: DAWN) ("Day One" or the "Company"), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported that the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) for tovorafenib as a monotherapy in relapsed or progressive pediatric low-grade glioma (pLGG) (Press release, Day One, OCT 30, 2023, View Source [SID1234636438]). The FDA has granted priority review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024. The FDA is not currently planning to hold an advisory committee meeting to discuss the application.

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pLGG is the most common brain tumor diagnosed in children, with patients suffering profound tumor and treatment-associated morbidities that can impact their life trajectory. For the vast majority of patients in the relapsed setting, there is no standard of care and no approved therapy.

"We are pleased to be one step closer to achieving our mission of bringing a novel targeted therapy to children whose low-grade gliomas with BRAF alterations have relapsed or progressed," said Jeremy Bender, Ph.D., chief executive officer of Day One. "We are grateful to the patients and their caregivers who participated in the FIREFLY-1 trial and look forward to continuing to collaborate with the FDA as we prepare to make this treatment more broadly available to those who need it."

The NDA is based on results from the open-label, pivotal Phase 2 trial evaluating tovorafenib as a once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG. Updated data was recently disclosed when the Company announced the completion of its rolling NDA submission on September 11, 2023. New, detailed data is expected to be presented at an upcoming medical conference.

Under the FDA’s Rare Pediatric Disease Priority Review Voucher program, the Company may receive a voucher if it receives an approval for an eligible indication, which can be redeemed to obtain priority review for a subsequent marketing application for a different product candidate.

Tovorafenib is an investigational therapy that is not approved for commercial use in any country.

About Pediatric Low-Grade Glioma

Pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30% – 50% of all central nervous systems tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pLGG. These genomic alterations are also found in severe adult and pediatric solid tumors.

Pediatric low-grade glioma can impact a child’s health in many ways depending on tumor size and location, including vision loss and motor dysfunction. There are no approved therapies for the vast majority of patients with pLGG, and current treatment approaches are associated with potential acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve remission following surgery may face years of increasingly aggressive treatment. Due to the indolent nature of pLGG, patients generally receive multiple years of systemic therapy.

About FIREFLY-1

FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG harboring a known activating BRAF alteration. The trial is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The primary endpoint is overall response rate (ORR), defined as the proportion of patients with confirmed response based upon Response Asessment for Neuro-Oncology High Grade Glioma (RANO-HGG) criteria. Secondary and exploratory endpoints include the overall response rate based on Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria, Response Assessment for Neuro-Oncology Low-Grade Glioma (RANO-LGG) criteria and volumetric analyses, progression-free survival, safety, functional outcomes, and quality of life measures. RANO-HGG, RANO-LGG and RAPNO-LGG are assessed by blinded independent central review. Additional information about FIREFLY-1 may be found at ClinicalTrials.gov, using Identifier NCT04775485.

About the Pacific Pediatric Neuro-Oncology Consortium

The Pacific Pediatric Neuro-Oncology Consortium (PNOC) is an international consortium with study sites within the United States, Canada, Europe and Australia dedicated to bringing new therapies to children and young adults with brain tumors.

About Tovorafenib

Tovorafenib is an investigational, oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 325 patients to date and is currently under evaluation in two pivotal clinical trials for pLGG. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1).

Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.