On August 19, 2024 Kelun reported that the new drug application (NDA) for the core product sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) based on the positive results from the pivotal OptiTROP-Lung03 study has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. ("Kelun-Biotech", 6990.HK) (Press release, Kelun, AUG 20, 2024, View Source [SID1234645995]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

OptiTROP-Lung03 is a multi-center, randomized, pivotal clinical study that evaluates sac-TMT monotherapy 5mg/kg every other week (Q2W) as an intravenous injection versus docetaxel for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who failed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy. At a pre-specified analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) and progression-free survival (PFS) compared with docetaxel.

Lung cancer mainly includes non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC is the most common pathological type, accounting for about 80%-85% of all lung cancers. The molecular typing of NSCLC patients in China is different from that of Western populations, and EGFR mutation is a common variant gene type, accounting for about 40%-50% of lung adenocarcinoma patients in China [1]. According to the 2024 CSCO guidelines, EGFR-TKIs are the preferred treatment for stage IV EGFR-mutant NSCLC [2]; platinum-containing chemotherapy is the main first-line chemotherapy regimen after resistance to EGFR-TKIs; and existing treatment regimens are ineffective in those who have failed EGFR-TKIs and platinum-containing chemotherapy. Single-agent chemotherapy is the current standard of care for this population, and docetaxel is the most commonly used single-agent chemotherapy, with an ORR of 3.2%-10.8%, a median PFS of only about 2 months, and a median OS of about 6-8 months [3,4,5,6,7]. For patients with locally advanced or metastatic EGFR-mutated NSCLC who have failed treatment with EGFR-TKIs and who have failed platinum-containing chemotherapy, the existing treatment regimens are less efficacious, there is a large unmet clinical need, and new drugs are urgently needed to improve patient survival.

Kelun-Biotech has filed the Application for sac-TMT for injection for the treatment of patients with locally advanced or metastatic EGFR-mutant NSCLC who failed after treatment with an EGFR-TKI and platinum-based chemotherapy.

The Application is the second NDA for sac-TMT that has been accepted by the NMPA. On August 14, 2024, it was announced on the official website of the CDE that the Application was planned to be included in the priority review and approval process of the CDE. Previously, an NDA for sac-TMT in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) was accepted by the NMPA.

Dr. Junyou Ge, CEO of Kelun-Biotech, said, "It is a great honor to have the second NDA of SKB264 accepted. Kelun-Biotech has always adhered to an innovation-driven development strategy, actively exploring cutting-edge technologies and new approaches to the treatment of major diseases. In response to unmet medical needs, we are committed to the original innovation of new drugs with differentiated advantages and international potential. By enhancing our end-to-end innovative drug development capabilities, we continuously improve the efficiency and success rate of drug research and development, and make every effort to move forward our clinical research progress. We are dedicated to continuously exploring and rapidly validating the clinical value of core projects. The company will always be guided by a caring heart, striving for excellence, and contributing to the great global oncology health cause."

On August 19, 2024 Daiichi Sankyo (TSE: 4568) reported that the European Medicines Agency (EMA) has validated the Type II Variation application for ENHERTU (trastuzumab deruxtecan) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting (Press release, AstraZeneca, AUG 19, 2024, View Source [SID1234645999]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. This application is based on data from the DESTINY-Breast06 phase 3 trial presented as a late-breaking oral session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO24) Annual Meeting.

"This submission builds on our existing indication for ENHERTU in patients with HER2 low metastatic breast cancer and an expanded approval would enable the potential for use in an earlier disease setting as well as in a broader patient population that now includes HER2 ultralow," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We look forward to working closely with the EMA to potentially bring this medicine to more patients in the EU."

Additional regulatory submissions for ENHERTU in this indication are underway globally.

About DESTINY-Breast06

DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab paclitaxel) in patients with HR positive, HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.

The primary endpoint is progression-free survival (PFS) in the HR positive, HER2 low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), overall survival (OS) in patients in the HER2 low patient population and OS in the overall trial population. Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance.

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About Breast Cancer and HER2 Expression

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually.2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.3

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer.4 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) are classified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to 20% percent of all breast cancers.5 Historically, tumors that were not classified as HER2 positive were classified as HER2 negative, despite the fact that many of these tumors still carry some level of HER2 expression.6 It is estimated that approximately 60% to 65% of HR positive, HER2 negative breast cancers are HER2 low and potentially an additional 25% may be HER2 ultralow.7,8

Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer.9 However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited.9 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.9,10,11,12

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2 low expression.13 There are no targeted therapies specifically approved for patients with HER2 ultralow expression.14

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Full approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population.

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.

On August 19, 2024 OS Therapies (NYSE American: OSTX) ("OS Therapies" or "the Company"), an ADC and Immunotherapy research and clinical-stage biopharmaceutical company, reported that it has been accepted into Johnson & Johnson Innovation – JLABS (Press release, OS Therapies, AUG 19, 2024, View Source;JLABS [SID1234645998]). Through membership of JLABS, OS Therapies aims to further develop and enter the clinic with its tunable Antibody Drug Conjugate (ADC) linker-based platform that relies on pH sensitive linkers & coating technology to reduce off-target effects to improve safety and increase the number & diversity of therapeutic payloads delivered. Through these developments, OS Therapies hopes to offer improved efficacy versus other ADCs in the market or in development. Drug candidates developed using OS Therapies’ tunable ADC platform leverage this unique linker platform to create new intellectual property for both novel and off-patent targeting antibodies and drug payloads.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On August 19, 2024 MOMA Therapeutics, a clinical-stage biopharmaceutical company discovering and developing a new generation of precision therapeutics, reported that the first patient has been dosed in its Phase 1 clinical trial to assess the safety and tolerability of MOMA-313, a novel, highly potent and selective oral polymerase theta helicase inhibitor (Press release, MOMA Therapeutics, AUG 19, 2024, View Source [SID1234645997]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

MOMA-313 is initially being developed in combination with a PARP inhibitor for patients with solid tumors harboring alterations in certain DNA repair genes, including subgroups of prostate cancer, pancreatic cancer and breast cancer.

In parallel, MOMA announced the selection of a development candidate for its second lead program, MOMA-341, an oral potent and selective covalent Werner helicase inhibitor for treatment of cancers with microsatellite instability. An IND application filing with the FDA is anticipated in the first quarter of 2025.

"We are excited to be progressing two molecules with best-in-class potential toward the benefit of cancer patients in need in such close proximity," said Asit Parikh, M.D., Ph.D., chief executive officer of MOMA. "The advance into clinical development for a company founded as an idea on paper a few years back is humbling. This progress serves as a testament to the excellence and unwavering commitment of the entire MOMA team."

"Advancing two highly potent and selective drug candidates derived from our proprietary KNOMATIC platform toward the clinic is a unique privilege," added Peter Hammerman, M.D., Ph.D., chief scientific officer of MOMA. "The goal with each candidate is to translate groundbreaking science into life-altering medicine."

About MOMA-313 and the Phase 1 Trial

MOMA-313 is a potent and selective oral polymerase theta (Polθ) helicase inhibitor. Polθ is involved in the repair of DNA double-strand breaks that arise during DNA replication. The Phase 1 trial (NCT06545942) is a multi-center, open-label study designed to evaluate the safety and tolerability of MOMA-313 as monotherapy and in combination with the PARP inhibitor olaparib for patients where a PARP inhibitor would be expected to provide benefit. Response to PARP inhibitors can be short-lived due to primary and acquired resistance. Pre-clinical studies suggest that combining a PARP inhibitor with a Polθ inhibitor could afford unique mechanistic potential to deepen and prolong that response.

About MOMA-341

MOMA is developing MOMA-341 as an oral, potent and selective covalent inhibitor of Werner helicase with a novel chemical scaffold as monotherapy and in combination with chemotherapy and immunotherapy in tumors with microsatellite instability (e.g., colorectal, gastric, endometrial cancers).

About the KNOMATIC platform

The KNOMATIC platform integrates deep structural insights, advanced hit-finding technologies, and computation-enabled lead optimization to accelerate discovery of novel therapeutics targeting families of highly dynamic proteins, such as ATPases and GTPases. MOMA-313 and MOMA-341 were discovered and developed through the application of the KNOMATIC platform.

On August 19, 2024 Scorpion Therapeutics, Inc. ("Scorpion"), a pioneering clinical-stage oncology company dedicated to transforming the lives of cancer patients by redefining the frontier of precision oncology, reported that it was selected to present initial, first-in-human clinical results from the Phase 1/2 study of STX-478, a mutant-selective PI3Kα inhibitor, in advanced solid tumor patients in a Proffered Paper late-breaking session at the European Society for Medical Oncology ("ESMO") Congress 2024, taking place September 13 – 17, 2024 in Barcelona, Spain (Press release, Scorpion Therapeutics, AUG 19, 2024, View Source [SID1234645996]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The presentation of first-in-human clinical data for our lead candidate, STX-478, marks an important milestone for patients living with advanced solid tumors driven by PI3Kα mutations, especially HR+/HER2- breast cancer, and for Scorpion as we work to broaden the reach and impact of precision oncology for patients with high unmet medical need," said Mark Chao, M.D., Ph.D., Chief Medical Officer of Scorpion. "While PI3Kα has been one of the highest profile targets in cancer for years, current treatment options suffer from toxicity limitations and subpar efficacy due to a lack of mutant selectivity. These initial data will provide early insight into how STX-478’s differentiated profile translates to potentially superior outcomes in PI3Kα-mutated cancers, and we look forward to presenting initial assessments of safety, pharmacokinetic and pharmacodynamic data and preliminary efficacy data at the ESMO (Free ESMO Whitepaper) 2024 Congress."

Details of the Proffered Paper presentation are as follows:

Title: First-in-human Results of STX-478, a Mutant-selective PI3Kα Inhibitor, in Advanced Solid Tumor Patients
Presentation Number: LBA27
Session Name: Proffered paper session 2: Developmental therapeutics (ID 156)
Session Date & Time: Sunday, September 15, 2024, at 14:45 CEST – 16:15 CEST (8:45 a.m. – 10:15 a.m. ET)
Presentation Time: 14:55 CEST – 15:05 CEST (8:55 a.m. – 9:05 a.m. ET)
Location: Salamanca Auditorium – Hall 5
Presenter: Alberto J. Montero, M.D. (University Hospitals Cleveland, OH, USA)

According to ESMO (Free ESMO Whitepaper), the late-breaking abstract will be published via the ESMO (Free ESMO Whitepaper) website at 00:05 CEST on September 15 (6:05 p.m. ET on September 14). Data presented at the conference will be available to view in the "Publications & Presentations" section of the Scorpion website (View Source) following the ESMO (Free ESMO Whitepaper) 2024 Congress.

About STX-478

STX-478 was designed to improve outcomes in patients harboring PI3Kα mutations, one of the most prevalent drivers of cancer, occurring in over 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. In preclinical models, STX-478 demonstrated robust activity across a range of PI3Kα mutations while sparing wild-type PI3Kα inhibition in normal tissues; previous generations of non-selective PI3Kα inhibitors have limited patient benefit due to these on-target toxicities. Scorpion’s Phase 1/2 clinical trial is a multi-center, global, open-label study designed to evaluate the safety and tolerability of STX-478 in multiple ascending doses for patients with locally advanced or metastatic HR+/HER2- breast cancer and other solid tumors driven by PI3Kα mutations. The program entered the clinic in 2023 and has rapidly advanced, now in multiple expansion cohorts across a range of solid tumors and in breast cancer as monotherapy and in combinations with fulvestrant and CDK4/6 inhibitors. To learn more about the first-in-human trial of STX-478, please visit this page.