On August 30, 2024 Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, reported that it has granted the China rights (including mainland China, Hong Kong, Macau, and Taiwan) of KRAS G12C inhibitor glecirasib and SHP2 inhibitor JAB-3312 to Shanghai Allist Pharmaceuticals Co., Ltd (688578.SH) (Press release, Jacobio Pharmaceuticals, AUG 30, 2024, View Source [SID1234646240]).

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According to the terms of the agreement, Jacobio shall receive around RMB200 million in the near term, which includes an upfront payment of RMB150 million, and around RMB50 million of compensation for research and development expenses and other payments. Additionally, the potential milestone payments upon achieving certain development, regulatory and commercial milestones are up to RMB700 million. Jacobio is also entitled to receive tiered double-digit royalty payments on net sales of glecirasib and JAB-3312 from Allist, among which the royalty payments on net sales of JAB-3312 is up to 20%. The above amount includes value-added tax. Allist will be responsible for the commercialization of glecirasib and JAB-3312 in China and pay the subsequent clinical development costs in China. This marks that Jacobio has officially entered the commercialization stage, and the research and development of SHP2 has also ushered in a new milestone.

Dr. Wang Yinxiang, Chairman and CEO of Jacobio, said: "We are delighted to reach this cooperation with Allist. Allist has strong commercialization capabilities in the field of lung cancer, and the first indication for glecirasib submitted the new drug application is lung cancer. We believe that with the deep fit of the advantages of both parties, this collaboration will demonstrate great clinical and commercial value. In addition to the cooperation with glecirasib, Allist also licensed-in the SHP2 inhibitor JAB-3312, which is the first SHP2 inhibitor entering a registrational trial globally. It is expected to become a first-line therapy in combo with glecirasib, which reflects Allist’s foresight into the future of pipelines. We also look forward to jointly accelerating the development and commercialization of the two products to meet the clinical needs of more patients. "

Jinhao Du, the Chairman and general manger of Allist, said: "we are please to cooperate with Jacobio, and the cooperation will surely benefit the growth of both companies. For many years, Allist has taken ‘Technology Cares for Life’ as our corporate mission, focusing on scientific exploration and drug development in the field of cancer therapies, and is committed to developing and introducing superior pipelines consisting of best-in-class and first-in-class drugs. While we successfully independently developed and launched furmonertinib, we have built a commercial team that focuses on lung cancer, has professional academic promotion capabilities, and has a wide sales channel coverage. Since its launch, furmonertinib has achieved remarkable sales performance. Jacobio is a very outstanding innovative biotech company that has successfully developed and promoted a number of excellent products with great clinical value, including the KRAS G12C inhibitor glecirasib and the SHP2 inhibitor JAB-3312. We are very optimistic about the clinical advantages and market prospects of these two products. In this cooperation, Allist will give full play to its advantages in clinical development and commercialization capabilities to benefit more Chinese patients and create value for both companies."

The new drug application for glecirasib monotherapy for second-line non-small cell lung cancer (NSCLC) with KRAS G12C mutation was granted priority review on May 21, 2024. In December 2022, it was granted breakthrough therapy designation (BTD) Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the second-line and above treatment of patients with advanced or metastatic NSCLC with KRAS G12C mutation. In April 2024, the data of the pivotal Phase II study of glecirasib published by Jacobio in the ASCO (Free ASCO Whitepaper) Plenary Series showed that in patients with second-line NSCLC, the confirmed objective response rate (cORR) was 47.9% (56/117), including 4 patients achieved a complete response (CR) and 36 patients with tumor reduction exceeding 50%. Disease control rate (DCR) was 86.3%. The median progression-free survival (mPFS) was 8.2 months, and median overall survival (mOS) was 13.6 months.

The first patient dosed in the Phase III clinical trial of KRAS G12C inhibitor glecirasib and SHP2 inhibitor JAB-3312 versus standard care (chemotherapy and anti-PD-1 antibody) in front-line KRAS G12C mutant NSCLC in August 2024. According to the Phase I/IIa data presented at the ASCO (Free ASCO Whitepaper) Annual Meeting, the optimal dose group was glecirasib at 800mg daily combined with JAB-3312 at 2mg daily one week on and one week off. The cORR of the optimal dose group was 77.4% (24/31), and 54.8% (17/31) of patients achieved a deep response with tumors shrinking by more than 50%. Regarding on the safety data, among the 194 all-dosage patients, the incidence of grade 3 or 4 treatment-related adverse events (TRAE) was 43.8%, and there was no treatment-related death. The overall safety is manageable.

In addition, the pivotal studies of glecirasib monotherapy for second-line or above pancreatic cancer, glecirasib monotherapy and in combination with cetuximab for colorectal cancer with are also undergoing. In terms of pancreatic cancer, in April 2024, glecirasib was granted orphan drug designation from Food and Drug Administration (FDA) for pancreatic cancer indications; in August 2023, it was granted BTD by CDE of NMPA for the treatment of second-line or above pancreatic cancer patients with KRAS G12C mutations. The combination of glecirasib and cetuximab for the treatment of colorectal cancer was approved for registrational phase III clinical trial in China in May 2024.

About Glecirasib
Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with cetuximab in colorectal cancer. The pancreatic cancer indication has obtained orphan drug designation in the United States and breakthrough therapy designation in China.

About JAB-3312
JAB-3312 is a highly selective SHP2 allosteric inhibitor with best-in-class potential. Jacobio is currently conducting clinical trials of JAB-3312 in monotherapy and combination therapies with glecirasib and other agents in China, the United States and Europe. The phase III study in combination with KRAS G12C inhibitor glecirasib has been approved by China CDE in Feb 2024.

On August 30, 2024 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that, on August 29, 2024, the Compensation Committee of IDEAYA’s Board of Directors granted non-qualified stock options to purchase an aggregate of 34,000 shares of the Company’s common stock to a newly hired employee (Press release, Ideaya Biosciences, AUG 30, 2024, View Source [SID1234646241]). The stock options were granted under the IDEAYA Biosciences, Inc. 2023 Employment Inducement Incentive Award Plan (2023 Inducement Plan) as an inducement material to such individual entering into employment with IDEAYA in accordance with Nasdaq Listing Rule 5635(c)(4).

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The 2023 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of IDEAYA, or following a bona fide period of non-employment, as an inducement material to such individuals’ entering into employment with IDEAYA, pursuant to Nasdaq Listing Rule 5635(c)(4).

The stock options have an exercise price of $39.17 per share, which is equal to the closing price of IDEAYA’s common stock on The Nasdaq Global Select Market on the date of grant. The stock options have a 10-year term and will vest over four years, with 25% of the options vesting on the first anniversary of the vesting commencement date and the remaining 75% of the options vesting in equal monthly installments over the three years thereafter. Vesting of the stock options is subject to such employee’s continued service to IDEAYA on each vesting date.

On August 29, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that Robert M. Davis, chairman and chief executive officer, and Dr. Dean Y. Li, executive vice president and president, Merck Research Laboratories, are scheduled to participate in a fireside chat at the Morgan Stanley 22nd Annual Global Healthcare Conference on Thursday, Sept. 5, 2024, at 2:35 p.m. EDT (Press release, Merck & Co, AUG 29, 2024, View Source [SID1234646204]).

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Investors, analysts, members of the media and the general public are invited to listen to a live audio webcast of the presentation at this weblink.

On August 29, 2024 Bayer reported that the first patient has been enrolled in the global Phase III SOHO-02 trial, an open-label, randomized, multicenter clinical trial, assessing the efficacy and safety of investigational agent BAY 2927088 as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC), whose tumors have activating HER2 mutations (Press release, Bayer, AUG 29, 2024, View Source [SID1234646222]).

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Beyond the SOHO-02 trial, investigational agent BAY 2927088 is also being assessed for its potential as a second-line therapy in adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and who have received a prior systemic therapy. Late-breaking results from the phase I/II SOHO-01 trial will be presented in the presidential symposium at the World Conference on Lung Cancer (WCLC) in San Diego on Monday, September 9th, 2024.

"Our commitment to precision medicine is not just a promise but a mission to address the critical unmet needs of individuals battling HER2-mutant NSCLC, a variant of the most prevalent form of lung cancer," said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. "By advancing innovative research, we are dedicated to improving survival rates for those affected by this devastating disease. This endeavor underscores our commitment to pioneering precise and personalized healthcare solutions for those in direct need."

Investigational agent BAY 2927088 is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.

Lung cancer is the leading cause of cancer-related deaths worldwide. Currently there are no approved targeted first-line therapies for patients with NSCLC harboring HER2 activating mutations.

BAY 2927088 has received Breakthrough Therapy designation in the second-line setting from the U.S. Food and Drug Administration (FDA) in February 2024. In June 2024, the Center for Drug Evaluation (CDE) in China also granted investigational agent BAY 2927088 Breakthrough Therapy designation for the same patient population.

About the SOHO-02 Study
SOHO-02 is a global Phase III, open-label, randomized, multicenter clinical trial, assessing the efficacy and safety of investigational agent BAY 2927088 as first-line therapy for adult patients with advanced non-small cell lung cancer (NSCLC), whose tumors have activating HER2 mutations. Participants will be randomized to either investigational agent BAY 2927088 or the current standard of care (cisplatin/carboplatin + pemetrexed + pembrolizumab). The primary endpoint of the study is progression free survival (PFS) measured by a blinded, independent, central review. Additional endpoints include overall response rate (ORR), duration of response (DoR) and evaluating the safety of investigational agent BAY 2927088. More information can be found at View Source

About Investigational Agent BAY 2927088
BAY 2927088 is an investigational agent and has not been approved by any health authority for use in any country, for any indication. It is currently being evaluated as a potential new targeted treatment option for patients with NSCLC harboring HER2 activating mutations. BAY 2927088 is an oral, reversible tyrosine kinase inhibitor (TKI) that potently inhibits mutant human epidermal growth factor receptors 2 (HER2), including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with high selectivity for mutant vs wild-type EGFR.

About Non-Small Cell Lung Cancer (NSCLC)
NSCLC is the most common type of lung cancer, accounting for more than 85% of cases. Activating HER2 mutations are found in 2% to 4% of advanced NSCLC. 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes it more difficult to treat.

On August 29, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported updates on two Phase 3 trials, KEYNOTE-867 and KEYNOTE-630 (Press release, Merck & Co, AUG 29, 2024, View Source [SID1234646187]). Merck is discontinuing the Phase 3 KEYNOTE-867 trial evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with stereotactic body radiotherapy (SBRT) for the treatment of patients with stage I or II (stage IIB N0, M0) non-small cell lung cancer (NSCLC), including those who are medically inoperable or have refused surgery. This decision is based on the recommendation of an independent Data Monitoring Committee (DMC), which reviewed data from a planned interim analysis. At the pre-specified interim analysis, KEYTRUDA in combination with SBRT did not demonstrate an improvement in event-free survival (EFS) or overall survival (OS), the study’s primary endpoint and key secondary endpoint, respectively, compared to placebo plus SBRT, and the benefit/risk profile of the combination did not support continuing the trial. KEYTRUDA in combination with SBRT was associated with higher rates of adverse events (AEs), including AEs leading to death, compared with SBRT and placebo.

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Merck is also discontinuing the Phase 3 KEYNOTE-630 trial evaluating KEYTRUDA for the adjuvant treatment of patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) following surgery and radiation, based on the recommendation of an independent DMC. The DMC recommended that the study should be stopped for futility as the risk/benefit profile did not support continuing the trial. Data from a pre-planned analysis showed that KEYTRUDA did not cross the boundary for statistical significance in recurrence-free survival (RFS), the study’s primary endpoint. The study’s key secondary endpoint, OS, was not formally tested, but at the time of the analysis, the results did not favor KEYTRUDA compared to placebo. The safety profile of KEYTRUDA in this trial was consistent with the established safety profile of KEYTRUDA.

Merck has informed study investigators and advises patients in the studies to speak to their study team and physician regarding next steps and treatment options. Data analyses for KEYNOTE-867 and KEYNOTE-630 are ongoing, and the results will be shared with the scientific community and regulatory agencies.

"Our understanding of cancer and how it can be treated has rapidly evolved in recent years, but unmet needs remain across different types of cancer and stages of disease," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet need, such as non-small cell lung cancer and cutaneous squamous cell carcinoma, with the goal to help even more patients. We are extremely grateful to all of the patients, caregivers and investigators for their participation in these studies."

About KEYNOTE-867

KEYNOTE-867 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03924869) evaluating KEYTRUDA plus SBRT compared to placebo plus SBRT for the treatment of adult patients with unresected stage I or II (stage IIB N0, M0) NSCLC. Patients in KEYNOTE-867 were medically inoperable, which included patients who could not undergo thoracic surgery due to existing medical illness(es) or anatomically unresectable tumor, or who decided to treat with SBRT as definitive therapy rather than surgery, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. The primary endpoint is EFS, and key secondary endpoints include OS and safety. EFS is defined as the time from randomization to the first occurrence of local, regional, or distant recurrence of disease, or death due to any cause. The trial enrolled an estimated 436 patients who were randomized 1:1 to receive either:

KEYTRUDA (200 mg) every three weeks (Q3W) for up to 17 cycles (up to approximately one year) plus SBRT once every three days for three, four, five or eight fractions (dependent on tumor type/location; 45-70 Gray total) over approximately two weeks; or
Placebo Q3W for up to 17 cycles (up to approximately one year) plus SBRT once every three days for three, four, five or eight fractions (dependent on tumor type/location; 45-70 Gray total) over approximately two weeks.
About KEYNOTE-630

KEYNOTE-630 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03833167) evaluating KEYTRUDA as adjuvant therapy in patients with high-risk locally advanced cSCC who have undergone surgery with or without positive margins and completed adjuvant radiotherapy compared to placebo. The primary endpoint is RFS, and key secondary endpoints include OS and safety. The trial enrolled an estimated 430 patients who were randomized to receive either:

KEYTRUDA (400 mg intravenously [IV] every six weeks [Q6W] for up to nine cycles) as adjuvant therapy following surgery and radiation; or
Placebo (IV Q6W for up to nine cycles) as adjuvant therapy following surgery and radiation.
About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.48 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

About cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma is the second most common non-melanoma skin cancer and forms in squamous cells, which are in the outer part of the epidermis. This type of skin cancer is usually caused by prolonged exposure to ultraviolet (UV) radiation, either from the sun or from artificial sources, such as tanning beds. Cutaneous squamous cell carcinoma is five times more prevalent than melanoma, and prevalence has been increasing for many years, likely due to better skin cancer detection, more sun exposure and people living longer. In the U.S., an estimated 1.8 million cases of cSCC are diagnosed each year, accounting for approximately 20% of all skin cancer cases.