On December 16, 2024 GSK plc (LSE/NYSE: GSK) reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for Jemperli (dostarlimab) for the treatment of patients with locally advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer (Press release, GlaxoSmithKline, DEC 16, 2024, View Source [SID1234649133]). The Breakthrough Therapy Designation aims to expedite the development and review of drugs with the potential to treat a serious condition and where preliminary clinical evidence may indicate substantial improvement over currently available therapy.1 This is the second regulatory designation for dostarlimab in locally advanced dMMR/MSI-H rectal cancer, following Fast Track designation for the same patient population in January 2023.2

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "Today’s designation, which is based on the unprecedented 100% clinical complete response rate of dostarlimab reported to date, supports a path to help change the treatment paradigm for patients with locally advanced dMMR/MSI-H rectal cancer, who face long-term adverse quality-of-life effects. Our registrational AZUR-1 trial is continuing to study dostarlimab in this patient population."

The US FDA’s Breakthrough Therapy Designation is supported by preliminary clinical evidence from the ongoing phase II GSK supported collaborative study with Memorial Sloan Kettering Cancer Center. In frontline locally advanced dMMR rectal cancer, the trial has shown an unprecedented 100% clinical complete response (cCR) in all 42 patients who completed treatment with dostarlimab, defined as no evidence of tumours as assessed by magnetic resonance imaging, endoscopy, PET scan and digital rectal exam. In the first 24 patients evaluated, a sustained cCR with a median follow-up of 26.3 months (95% CI: 12.4-50.5) was observed. The safety and tolerability profile of dostarlimab was generally consistent with the known safety profile of the agent. No adverse events of grade 3 or higher were reported in this trial.3 The trial continues to evaluate enrolled patients. GSK’s ongoing phase II registrational AZUR-1 trial in locally advanced dMMR/MSI-H rectal cancer aims to confirm the findings of this supported collaborative study.

The current standard of care for patients with dMMR/MSI-H locally advanced rectal cancer is initial treatment with chemotherapy plus radiation followed by surgery to remove the tumour along with portions of the intestine and/or surrounding tissue.4 This results in initial positive outcomes for most patients, but nearly one-third ultimately die from cancer that has spread to other parts of the body (distant metastasis).5 Additionally, the surgery and chemoradiotherapy associated with standard of care can lead to long-term negative impact on quality-of-life, including bowel, urinary and sexual dysfunction, secondary cancers and infertility.2

Dostarlimab is not approved anywhere in the world for the frontline treatment of locally advanced dMMR/MSI-H rectal cancer.

About dMMR/MSI-H rectal cancer
Rectal cancer is a form of cancer that starts in the rectum, the final section of the large intestine, and is often categorised as part of a group of cancers called colorectal cancer. Colorectal cancer is the third most commonly diagnosed cancer in the world.6 In the US, it is estimated that approximately 46,220 individuals are diagnosed annually with rectal cancer.7 Approximately 5-10% of all rectal cancers are dMMR/MSI-H, meaning that they contain abnormalities that affect the proper repair of DNA when copied in a cell.8 Mismatch repair deficient status is a biomarker that has been shown to predict response to immune checkpoint blockade with PD-1 therapy.9,10 Tumours with this biomarker are most commonly found in endometrial, colorectal and other gastrointestinal cancers but may also be found in other solid tumours.11-14

About Jemperli (dostarlimab) 
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.

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. This includes patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with 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. Additionally, Jemperli is 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. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist. 

Important Information for Jemperli in the EU
Jemperli is indicated:

in combination with carboplatin and paclitaxel, for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;
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 December 16, 2024 GSK plc (LSE/NYSE: GSK) reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended expanding the approval of Jemperli (dostarlimab) in combination with chemotherapy (carboplatin and paclitaxel) for first-line treatment of all adult patients with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy (Press release, GlaxoSmithKline, DEC 16, 2024, View Source [SID1234649132]). This would include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours, who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options.

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The CHMP opinion is one of the final steps prior to a marketing authorisation decision by the European Commission, with an approval decision expected in the first quarter of 2025.

The application to expand the use of dostarlimab is based on results from Part 1 of the RUBY phase III trial. The trial met its dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS), demonstrating a statistically significant and clinically meaningful benefit in the full population of patients treated with dostarlimab plus carboplatin-paclitaxel versus chemotherapy alone. Dostarlimab plus chemotherapy is the only immuno-oncology-based regimen to show a statistically significant OS benefit in this patient population. The safety and tolerability analyses from RUBY showed a safety profile for dostarlimab plus carboplatin-paclitaxel that was consistent with the known safety profiles of the individual agents.

OS data were presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer on 16 March 2024, and were published in Annals of Oncology on 9 June 2024. The label for Jemperli in the US was expanded to all adult patients with primary advanced or recurrent endometrial cancer in August 2024.

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,1 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.2 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.3 In Europe, approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer each year.4  Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumours.6

About RUBY  
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of 785 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.

In Part 1, the dual-primary endpoints 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 overall 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 in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology. 

About Jemperli (dostarlimab) 
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.

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. This includes patients with MMRp/MSS and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with 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. Additionally, Jemperli is 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. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist. 

Important Information for Jemperli in the EU
Indication
Jemperli is indicated:

in combination with carboplatin and paclitaxel, for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;
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 December 16, 2024 GSK plc (LSE/NYSE: GSK) reported that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) Designation for GSK5764227 (GSK’227), its B7-H3-targeted antibody-drug conjugate (ADC) being evaluated for the treatment of patients with relapsed extensive-stage small-cell lung cancer (ES-SCLC) (Press release, GlaxoSmithKline, DEC 16, 2024, View Source [SID1234649131]). The PRIME Designation supports the development of medicines with potential to offer a major therapeutic advantage for patients.1 This is the second regulatory designation for GSK’227, following the US Food and Drug Administration’s decision to grant Breakthrough Therapy Designation in August 20242.

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "This PRIME Designation is an important step forward as we seek to accelerate development of GSK’227 in extensive-stage small-cell lung cancer and other tumour types with limited treatments. Our investigational B7-H3-targeted ADC is a key component of our broader ADC programme."

The EMA’s PRIME Designation is supported by preliminary clinical data from the ARTEMIS-001 study. This is an ongoing phase I open-label, multi-centre trial of more than 200 patients evaluating the safety, tolerability, and preliminary anti-tumour activity in locally advanced or metastatic solid tumours, including relapsed ES-SCLC, conducted by Hansoh Pharma. The efficacy and safety results from this trial were presented at the 2024 World Conference on Lung Cancer earlier this year. GSK recently began a global phase I trial to support a registrational pathway for GSK’227.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide.3 In Europe, there were an estimated 484,554 new cases and 375,784 deaths from lung cancer in 2022.4 SCLC represents 10-15% of all lung cancer cases and is among the deadliest subtypes.5,6 ES-SCLC constitutes 60% to 85% of all SCLC cases at diagnosis and is characterised by tumours that have spread beyond the lungs.7 Platinum resistant or refractory patients typically have very poor outcomes, with median overall survival of less than six months.8,9

Earlier this year, GSK acquired exclusive worldwide rights (excluding China’s mainland, Hong Kong, Macau, and Taiwan) from Hansoh to progress clinical development and commercialisation of GSK’227.10

About GSK’227
GSK’227, also known as HS-20093, is a novel investigational B7-H3-targeted ADC composed of a fully human anti-B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor (TOPOi) payload. HS-20093 is being developed by Hansoh Pharma for the treatment of lung cancer, sarcoma, head and neck cancers and other solid tumours in multiple phase I, II and III clinical trials in China. GSK’s global phase I trial for GSK’227 began in August 2024.

On December 16, 2024 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it has completed the Phase 1 dose escalation portion of the Acclaim-3 clinical trial of Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as maintenance therapy to treat patients with extensive stage small cell lung cancer (ES-SCLC) (Press release, Genprex, DEC 16, 2024, View Source [SID1234649130]). In addition, the Safety Review Committee (SRC) has approved the opening of the Phase 2 expansion portion of the trial.

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The combination of REQORSA and atezolizumab previously received U.S. Food and Drug Administration’s (FDA) Fast Track Designation for the treatment of the Acclaim-3 patient population, and the FDA has also granted Orphan Drug Designation to REQORSA for the treatment of SCLC.

Based on full safety data, which showed no dose limiting toxicities (DLTs), the SRC determined that the Recommended Phase 2 Dose (RP2D) of REQORSA will be 0.12 mg/kg. This was the highest dose level delivered in the Phase 1 portion of the trial. The SRC also recommended the trial advance to the Phase 2 expansion portion of the study, which the Company has now opened for enrollment.

"We are pleased to complete the Phase 1 dose escalation portion of the Acclaim-3 clinical trial and to have now opened the Phase 2 expansion portion of Acclaim-3 for enrollment in the second half of 2024, in accordance with our previously disclosed guidance for timing and milestones," said Ryan Confer, President and Chief Executive Officer at Genprex. "Our partnership with a large network of community-based oncology practices has allowed us to have successful enrollment rates, enabling Genprex to meet our 2024 timeline targets for this study. In adding multiple clinical trial sites to our Acclaim-3 study, we have been able to more efficiently and expeditiously accelerate the Acclaim-3 clinical trial. Looking ahead, we believe this sets the stage for potential promising enrollment rates for the Phase 2 portion of the trial. Additionally, we will be submitting the results of the Phase 1 portion of the study to a clinical meeting and anticipate data presentation in 2025, and we remain encouraged by the early efficacy demonstrated in ES-SCLC patients."

Genprex previously reported the first patient treated in the Phase 1 dose escalation portion of the Acclaim-3 trial had a partial remission, which is defined as at least a thirty percent (30%) decrease in tumor size, from prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. A CT scan performed after four cycles of maintenance therapy (three months), confirmed that the patient had a 30% decrease in tumor size in measurable lesions; however, one lesion not previously measurable had grown in size, thus leading to a conclusion of disease progression at that time. As the maintenance therapy consists of REQORSA and Tecentriq, and the patient had already received four cycles of Tecentriq during induction therapy and thus responses to Tecentriq would likely have occurred earlier, the Company believes this suggests that REQORSA may be providing clinical benefit.

In the Phase 1 dose escalation portion of the Acclaim-3 clinical trial, patients were treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity was experienced. The primary endpoint of the Phase 1 escalation portion was to determine the Maximum Tolerated Dose (MTD) or RP2D.

The SRC is comprised of three physicians who are principal investigators in the trial. Based on the preliminary safety data from patients in the 0.12 mg/kg dose level, the SRC recommended that the 0.12 mg/kg dose be the RP2D that will be used in the Phase 2 portion of the trial and that the Phase 2 trial be opened for enrollment.

The Phase 1 dose escalation portion of the trial had two dose groups: 0.09 mg/kg and 0.12 mg/kg.The Phase 2 expansion portion will enroll approximately 50 patients at approximately 10 to 15 U.S sites. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. The primary endpoint of the Phase 2 portion is to determine the 18-week progression-free survival rate from the time of the start of maintenance therapy with REQORSA and Tecentriq in patients with ES-SCLC. Patients will also be followed for survival. A Phase 2 futility analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up.

Data presented at the October 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) from studies in humanized mouse models of SCLC that use human H841 cells have shown that the combination of REQORSA and Tecentriq provides significantly better control of tumor burden than either agent alone. The data from these studies also suggest that a combination treatment of REQORSA and Tecentriq can promote a significantly increased tumor cell killing effect in SCLC xenografts compared to that of Tecentriq alone.

About Acclaim-3

The Acclaim-3 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, Reqorsa Gene Therapy, in combination with Genentech, Inc.’s Tecentriq (atezolizumab) as maintenance therapy in patients with extensive stage small cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment.

On December 16, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported that David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene, will present at the 43rd Annual J.P. Morgan Healthcare Conference at the Westin St. Francis in San Francisco (Press release, Allogene, DEC 16, 2024, View Source [SID1234649124]).

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43rd Annual J.P. Morgan Healthcare Conference
Wednesday, January 15, 2025
3:00PM PT/ 6:00PM ET

A live audio webcast of the presentation will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section.

Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.