On October 20, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported results from the Phase 3 KEYNOTE-671 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as a perioperative treatment regimen, which includes treatment before surgery (neoadjuvant) and after surgery (adjuvant), for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC) (Press release, Merck & Co, OCT 20, 2023, View Source [SID1234636181]). These late-breaking data are being presented for the first time today during a proffered paper session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (abstract #LBA56).

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At the trial’s prespecified second interim analysis with a median follow-up of 36.6 months (range, 18.8 to 62.0), neoadjuvant KEYTRUDA plus chemotherapy followed by KEYTRUDA as a single agent after surgical resection significantly improved overall survival (OS), reducing the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; one-sided p=0.00517) in patients with resectable stage II, IIIA or IIIB NSCLC versus neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, regardless of PD-L1 expression. For patients who received the KEYTRUDA-based regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. The 36-month OS rates were 71.3% for patients who received the KEYTRUDA-based regimen versus 64.0% for patients who received the chemotherapy-placebo regimen.

As previously announced, KEYNOTE-671 met the trial’s other dual primary endpoint of event-free survival (EFS) at the first interim analysis of the study. At this second interim analysis, the EFS benefit observed in the previous interim analysis was maintained and the KEYTRUDA arm improved median EFS by nearly two and half years compared to the placebo and chemotherapy arm (47.2 months [95% CI, 32.9-NR] versus 18.3 months [95% CI, 14.8-22.1], respectively; HR=0.59 [95% CI, 0.48-0.72]). The 36-month EFS rates were 54.3% for patients who received the KEYTRUDA-based regimen versus 35.4% for patients who received the chemotherapy-placebo regimen.

"The results of KEYNOTE-671 represent an important milestone in our fight to improve treatment outcomes for patients with surgically resectable non-small cell lung cancer. The addition of perioperative KEYTRUDA to the standard of chemotherapy followed by surgery reduced the risk of death by 28% compared to placebo," said Dr. Jonathan Spicer, Associate Professor of Surgery at the McGill University Health Center and KEYNOTE-671 investigator. "Non-small cell lung cancer is the leading cause of cancer-related death worldwide and this new regimen applies to a wide range of surgically resectable patients. Hence, the introduction of KEYTRUDA to the standard of care of these patients could be a powerful tool for healthcare professionals to help extend the lives of patients."

"With these unprecedented survival data from KEYNOTE-671, KEYTRUDA is the first and only anti-PD-1/L1 therapy to demonstrate a statistically significant improvement in overall survival as a neoadjuvant and adjuvant treatment compared to a placebo and chemotherapy regimen for resectable non-small cell lung cancer," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "While KEYTRUDA has been established as a foundational treatment in certain advanced lung cancers, these overall survival results support the role of KEYTRUDA for patients with earlier stages of this disease, who are in need of new treatment options that may help them live longer."

Merck previously announced that, based on OS and EFS results from KEYNOTE-671, the U.S. Food and Drug Administration (FDA) approved KEYTRUDA for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC and small cell lung cancer (SCLC) include KEYNOTE-671, KEYNOTE-091, KEYNOTE-867, KEYLYNK-012, KEYLYNK-013 and KEYVIBE-006.

As announced, data spanning more than 15 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at ESMO (Free ESMO Whitepaper) Congress 2023.

Study design and additional data from KEYNOTE-671
KEYNOTE-671 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC (per the eight edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual). The trial’s dual primary endpoints are EFS, per RECIST v1.1 by investigator assessment, and OS. Key secondary endpoints include pCR and major pathological response (mPR). The study enrolled 797 patients who were randomly assigned (1:1) to receive either:

KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W]) plus chemotherapy (cisplatin [75 mg/m2, IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
Placebo (saline IV Q3W) plus chemotherapy (cisplatin [75 mg/m2, IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
Treatment-related adverse events (TRAEs) that were Grade ≥3 occurred in 45.2% of patients who received the KEYTRUDA-based regimen and 37.8% of patients who received the chemotherapy-placebo regimen. Treatment-related adverse events led to discontinuation of all study treatment in 13.6% of patients who received the KEYTRUDA-based regimen and 5.3% of patients who received the chemotherapy-placebo regimen. Treatment-related AEs led to death in 1.0% of patients who received the KEYTRUDA-based regimen and 0.8% of patients who received the chemotherapy-placebo regimen. No new safety concerns were identified.

About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and approximately 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% improvement over the last five years. Improved survival rates are due, in part, to advances in diagnostic and surgical procedures, as well as the introduction of new therapies. However, screening, early detection and improving treatment rates remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible were screened for lung cancer.

On October 20, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported results from the pivotal Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with external beam radiotherapy (EBRT) plus concurrent chemotherapy, followed by brachytherapy (also known as concurrent chemoradiotherapy) for newly diagnosed patients with high-risk locally advanced cervical cancer (stage 1B2-2B with lymph node-positive disease, and stage 3-4A with and without lymph node-positive disease) (Press release, Merck & Co, OCT 20, 2023, View Source [SID1234636180]). Results from the trial showed that KEYTRUDA in combination with concurrent chemoradiotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to concurrent chemoradiotherapy alone for these patients. The findings are being presented for the first time today at 10:45 a.m. ET during a late-breaking abstract proffered paper session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (abstract #LBA38).

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After a median follow-up of 17.9 months (range, 0.9-31.0), the KEYTRUDA regimen reduced the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.55-0.89]; p=0.0020) versus concurrent chemoradiotherapy alone in these patients. Median PFS was not reached in either group. The 24-month PFS rate was 67.8% for patients who received the KEYTRUDA regimen compared to 57.3% for those who received concurrent chemoradiotherapy alone. In addition to an improvement in PFS, a favorable trend in overall survival (OS), the trial’s other primary endpoint, was observed for the KEYTRUDA regimen versus concurrent chemoradiotherapy alone (HR=0.73 [95% CI, 0.49-1.07]); with only 103 events across both groups, these OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial is continuing, and follow-up of OS is ongoing. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified.

"Cervical cancer is the fourth most common cancer in women worldwide; however, over the past two decades, new treatment advances have been limited for patients diagnosed with locally advanced disease," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "These positive results from the KEYNOTE-A18 trial demonstrate the potential of KEYTRUDA in combination with concurrent chemoradiotherapy as a new treatment option for patients with high-risk cervical cancer, building on the established role of KEYTRUDA for certain patients with advanced cervical cancer and our research efforts in earlier stages of disease."

"This is the first phase 3 study in which an immunotherapy has demonstrated an improvement in progression-free survival in this patient population compared to standard of care," said professor Domenica Lorusso, the study’s overall principal investigator, lead investigator for ENGOT and associate professor of Obstetrics and Gynecology at the Catholic University of Rome. "The results of this trial, finding the KEYTRUDA regimen reduced the risk of disease progression or death by 30% compared to concurrent chemoradiotherapy alone, are compelling, especially considering newly diagnosed patients with high-risk locally advanced cervical cancer have not seen an advance in treatment options in 20 years."

"Patients diagnosed with locally advanced cervical cancer face a poor prognosis and limited treatment options," said Dr. Bradley Monk, oncologist and professor of obstetrics and gynecology at University of Arizona’s College of Medicine and Creighton University School of Medicine. "These results demonstrate that by moving an immunotherapy regimen to earlier stages of cervical cancer, we have the potential to improve outcomes for these patients compared to the current standard of care."

Merck previously announced that based on these positive results, the U.S. Food and Drug Administration (FDA) has granted priority review for a supplemental Biologics License Application (sBLA) for KEYTRUDA in combination with concurrent chemoradiotherapy for the treatment of newly diagnosed patients with high-risk locally advanced cervical cancer. The FDA has set a Prescription Drug User Fee Act, or target action, date of January 20, 2024. The results are also being discussed with regulatory authorities worldwide.

In the U.S., KEYTRUDA has two approved indications in cervical cancer: in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved test; and as a single agent, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

As announced, data spanning more than 15 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO (Free ESMO Whitepaper) Congress 2023.

Study design and additional data from KEYNOTE-A18/ENGOT-cx11/GOG-3047

KEYNOTE-A18, also known as ENGOT-cx11/GOG-3047, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04221945) sponsored by Merck and conducted in collaboration with the European Network for Gynaecological Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG) evaluating KEYTRUDA in combination with EBRT plus concurrent chemotherapy (cisplatin), followed by brachytherapy (also known as concurrent chemoradiotherapy) compared to placebo plus concurrent chemoradiotherapy for the treatment of newly diagnosed high-risk (stage 1B2-2B with lymph node-positive disease, and stage 3-4A with and without lymph node-positive disease) locally advanced cervical cancer where patients are treated with definitive intent. The primary endpoints are PFS and OS, and secondary endpoints include complete response rate, objective response rate and safety. The trial enrolled 1,060 patients who were randomized to receive:

KEYTRUDA (200 mg intravenously [IV]) on Day 1 of each three-week cycle (Q3W) for five cycles followed by KEYTRUDA (400 mg by IV) on Day 1 of each six-week cycle (Q6W) for an additional 15 cycles plus concurrent chemoradiotherapy (cisplatin 40 mg/m2 by IV once per week [QW] for five or six weeks plus EBRT followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units [Gy] for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days [with an extension to a maximum of 56 days for unforeseen delays]); or
Placebo plus concurrent chemoradiotherapy (cisplatin 40 mg/m2 by IV QW for five or six weeks plus EBRT followed by brachytherapy with minimum total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days [with an extension to a maximum of 56 days for unforeseen delays]).
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Treatment-related adverse events (TRAEs) occurred in 96% of patients receiving the KEYTRUDA regimen and 96% of patients receiving the placebo regimen; Grade 3-5 TRAEs occurred in 67.0% versus 60.6%, respectively. Treatment-related adverse events led to discontinuation of all study treatment in 0% of patients treated with the KEYTRUDA regimen and 0.2% treated with the placebo regimen. Additionally, TRAEs led to death in two (0.4%) patients receiving the KEYTRUDA regimen and two (0.4%) patients receiving the placebo regimen. No new safety concerns were identified.

Immune-mediated adverse events (AEs) of any grade occurred in 32.6% of patients receiving the KEYTRUDA regimen and 11.7% of patients receiving the placebo regimen. Grade 3-5 immune-mediated AEs occurred in 4.2% versus 1.1%, respectively. The most common of these all-grade immune-mediated AEs (occurring in more than two patients) was hypothyroidism (19.3%) in patients receiving the KEYTRUDA regimen. Immune-mediated AEs did not lead to death in either arm.

On October 20, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that the Company approved the grant of inducement stock options covering an aggregate of 48,300 shares of Iovance’s common stock to ten new non-executive employees (Press release, Iovance Biotherapeutics, OCT 20, 2023, View Source [SID1234636179]).

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The awards were granted under Iovance’s 2021 Inducement Plan, which was adopted on September 22, 2021 and amended on January 12, 2022 and May 10, 2023, and provides for the granting of equity awards to new employees of Iovance by the Company’s compensation committee in accordance with Nasdaq Listing Rule 5635(c)(4). Each of the stock options granted as referenced in this press release has an exercise price of $3.33, the closing price of Iovance’s common stock on the Date of Grant. Each stock option vests over a three-year period, with one-third of the shares vesting on the first anniversary of the employee’s start date (referred to as the "First Vesting Date"), and the remaining shares vesting in eight quarterly installments over the next two years, commencing with the first quarter following the First Vesting Date, subject to continued employment with the Company through the applicable vesting dates.

On October 20, 2023 GSK plc (LSE/NYSE: GSK) and Hansoh Pharma (HKEX: 03692), a Chinese biopharmaceutical company committed to discovering and developing life-changing medicines to help patients conquer serious diseases and disorders, reported that they have entered into an exclusive license agreement for HS-20089, a B7-H4 targeted antibody-drug conjugate (ADC) currently in phase I (NCT05263479) clinical trials in China (Press release, GlaxoSmithKline, OCT 20, 2023, View Source [SID1234636177]). Under the agreement, GSK will obtain exclusive worldwide rights (excluding China’s mainland, Hong Kong, Macau, and Taiwan) to progress development and commercialisation of HS-20089.

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Hesham Abdullah, SVP, Global Head Oncology, R&D, GSK, said: "Given early clinical data, we believe that HS-20089 has best-in-class potential in ovarian and endometrial cancer with opportunities in other solid tumours. This agreement is in line with our approach to advancing novel treatment options for patients with gynaecologic cancers."

In addition to targeting the B7-H4 surface antigen, which is overexpressed in ovarian and endometrial cancers and is often associated with poor prognosis, HS-20089 utilises clinically validated ADC technologies such as a topoisomerase inhibitor (TOPOi) payload.1 TOPOi is a validated mechanism of action in approved anti-cancer medicines and a proven standard of care in the treatment of breast and ovarian cancers.

Eliza Sun，Executive Director of Board, Hansoh Pharma, said: "In line with our commitment to deliver first- or best-in-class medicines to address unmet medical needs, Hansoh is excited to explore further development of HS-20089 to bring breakthrough medicines to cancer patients. GSK’s R&D expertise and commercial footprint in developing therapies for gynaecologic cancers make them the ideal licensee to bring HS-20089 to patients outside of China."

This agreement builds on GSK’s strategic R&D focus on tumour-cell targeting modalities as well as expertise in gynaecologic cancers including a significant medical and commercial presence. HS-20089 complements GSK’s oncology portfolio and strategic disease area focus, including potential future combinations.

GSK plans to begin phase I trials outside of China in 2024.

Terms of the agreement

Under the terms of this agreement, GSK will pay an $85 million upfront payment. In addition, Hansoh will be eligible to receive up to $1.485 billion in success-based milestones for HS-20089. Upon commercialisation of HS-20089, GSK will also pay tiered royalties on global net sales outside of China’s mainland, Hong Kong, Macau, and Taiwan.

This agreement is subject to appropriate regulatory agency clearances, including under the Hart-Scott-Rodino Act in the US.

About HS-20089

HS-20089 is a novel B7-H4 directed antibody-drug conjugate (ADC) with a topoisomerase inhibitor (TOPOi) payload. B7-H4, a transmembrane glycoprotein in the B7 superfamily, has limited expression in normal tissues but is highly expressed in various cancers. HS-20089 is being developed for the treatment of gynaecologic cancers in a phase I clinical study in China.

On October 20, 2023 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 will host a virtual key opinion leader (KOL) event highlighting the current state of lung cancer treatments and the challenges facing patients (Press release, Genprex, OCT 20, 2023, View Source [SID1234636176]).

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Event details are as follows:

Bringing Gene Therapy to the Fight Against Lung Cancers

Date and Time: October 27, 2023 at 12:30 pm – 1:45 pm ET

Webinar Registration Link: Click Here

The event will feature discussion with:

Alexander I. Spira, MD, PhD, FACP, Director of the Virginia Cancer Specialists (VCS) Research Institute and the Phase I Trial Program at Johns Hopkins Hospital; a medical oncologist who specializes in the treatment of lung cancers.
Daniel Morgensztern, MD, Professor of Medicine, and Director of Thoracic Oncology at Washington University School of Medicine; a medical oncologist who specializes in the treatment of lung and esophageal cancers.
The event will be moderated by Mark S. Berger, MD, Chief Medical Officer at Genprex, and will highlight REQORSA (quaratusugene ozeplasmid) as a potential treatment for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The webinar will conclude with a question and answer session with the audience.

A webcast of the event will be available on the investor relations page of the Genprex website at Videos Archive – Genprex. A replay of the webcast will be archived on Genprex’s website for a period of time.

About REQORSA Immunogene Therapy

REQORSA (quaratusugene ozeplasmid) for NSCLC and SCLC consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (Genprex’s ONCOPREX Nanoparticle Delivery System) with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells, which generally have a negative electrical charge. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing its uptake by normal tissue. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.