On December 9, 2024 Peptomyc reported the approval of a Research Investigational New Drug (IND) application for a groundbreaking Window of Opportunity trial in collaboration with Oregon Health & Science University (OHSU) Knight Cancer Institute and Brenden-Colson Center for Pancreatic Care (BCCPC) (Press release, Peptomyc, DEC 9, 2024, View Source [SID1234648991]). This trial will evaluate the pharmacodynamic effects of OMO-103 in patients with pancreatic ductal adenocarcinoma (PDAC). The study aims to expedite drug development, improve understanding of pharmacodynamic parameters, and identify biomarkers for better patient selection.

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Dr. Manuela Niewel, Chief Medical Officer at Peptomyc, stated, "This collaboration with OHSU Knight Cancer Institute and BCCPC represents a significant step forward in our mission to develop more effective, personalized cancer treatments. The Window of Opportunity trial design allows us to gather crucial data on our investigational compound, potentially accelerating the drug development process."

This partnership combines Peptomyc’s expertise in anti-MYC mini-proteins (namely the investigational drug OMO-103) with OHSU’s state-of-the-art research facilities and multidisciplinary approach to cancer treatment.

"We are excited to collaborate with Peptomyc on this important trial," said Dr. Charles Lopez, Principal Investigator at OHSU Knight Cancer Institute and BCCPC. "By conducting this study, we hope to gain valuable insights that will ultimately lead to improved outcomes for cancer patients."

The trial is expected to begin enrollment in March 2025 and will focus on ≥18-year-old patients with advanced PDAC.

About PDAC

PDAC is an aggressive form of cancer with a poor prognosis and increasing incidence. It accounts for over 85% of all solid pancreatic tumors. The 5-year relative survival rate is only about 11% for all stages and 3% for metastatic disease. PDAC is characterized by late detection and particularly aggressive biology, which contribute to its dismal outcomes. Surgical resection followed by adjuvant chemotherapy is the only potentially curative treatment, but it is only possible for 10-20% of patients.

Given these challenges, PDAC remains a critical area for oncological research and innovative treatment approaches.

About MYC

MYC is the most dysregulated oncogene in human cancer, controlling multiple transcriptional programs associated to most hallmarks of cancers, including increased proliferation, metastatic potential, immune suppression and resistance to treatment.

About OMO-103

OMO-103 is a first-in-class and best-in-class mini-protein against MYC. It has successfully been tested in a Phase Ia study in all-comers solid tumors and is currently in a Phase Ib study in metastatic PDAC patients in combination with standard of care chemotherapy.

On December 10, 2024 Keros Therapeutics, Inc. ("Keros" or the "Company") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta ("TGF-ß") family of proteins, reported that it presented additional data from its two ongoing Phase 2 clinical trials of elritercept (KER-050), one in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes ("MDS") and one in patients with myelofibrosis ("MF"), at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition ("ASH"), held in person in San Diego, California and virtually from December 7-10, 2024 (Press release, Keros Therapeutics, DEC 9, 2024, View Source [SID1234648987]).

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"The data we presented at ASH (Free ASH Whitepaper) supports the differentiated profile of elritercept in both MDS and MF," said Jasbir S. Seehra, Ph.D., Chair and Chief Executive Officer. "We look forward to commencing enrollment of our Phase 3 RENEW clinical trial evaluating elritercept in adult patients with transfusion-dependent anemia with very low-, low-, or intermediate-risk MDS soon, so that we can take the next step towards bringing this potential treatment option to patients."

Clinical Presentations

•Improvements in Hematological Parameters and Quality of Life ("QoL") with Elritercept: Results from an Ongoing Phase 2 Trial in Participants with Lower-Risk MDS

This ongoing, open-label, two-part, Phase 2 clinical trial is evaluating elritercept in patients with very low-, low-, or intermediate-risk MDS. As of August 30, 2024 (the "data cut-off date"), 95 patients had received at least one dose of elritercept at the recommended Part 2 dose ("RP2D") (collectively, the "safety population"). Of these patients in the safety population, 87 had completed at least 24 weeks of treatment or discontinued as of the data cut-off date (collectively, the modified intent-to-treat 24-week population, or the "mITT24 patients"). Data for hematological response and markers of hematopoiesis were presented from exploratory analyses of these mITT24 patients. All data presented from this trial is as of the data cut-off date.

Of the 95 patients in the safety population, 60.0% (n=57) were high transfusion burden ("HTB") while 24.2% (n=23) were low transfusion burden and 15.8% (n=15) were non-transfused ("NT").
Elritercept was generally well-tolerated in the safety population. There were four cases of fatal treatment-emergent adverse events ("TEAEs") in the trial that were all deemed unrelated to treatment. The most commonly reported TEAEs (in ≥15% of patients) were diarrhea, fatigue, COVID-19, dyspnea, dizziness, anemia, nausea and epistaxis. One patient had progressed to acute myeloid leukemia as of the data cutoff date.

55.2% (n=48/87) of the mITT24 patients achieved an overall erythroid response over the first 24 weeks of treatment, which is defined as meeting either modified International Working Group 2006 Hematological improvement-erythroid ("HI-E") or transfusion independence ("TI") for at least eight weeks in transfusion-dependent patients who required ≥ 2 red blood cell ("RBC") units transfused at baseline. The median duration of transfusion independence was 134.1 weeks. Due to ongoing TI responses as of the data cutoff date, the median duration of TI is expected to change as data continues to accumulate. 48.1% (n=13/27) of patients with a TI response had ongoing TI as of the data cutoff date, of which 92.3% (n=12/13) had ongoing TI for greater than 52 weeks.

Additional data from the mITT24 patients include:

•39.1% (n=27/69) of the TI-evaluable patients achieved TI for at least eight weeks over the first 24 weeks of treatment.
•Of the patients with HTB, 31.4% (n=16/51) achieved TI for at least eight weeks during the first 24 weeks of treatment. Eight of those 16 patients (50.0%) achieved TI for at least 24 weeks over the first 48 weeks of treatment.
•Of the TI-evaluable patients with baseline erythropoietin level less than 500 U/L, 47.3% (n=26/55) achieved TI for at least eight weeks over the first 24 weeks of treatment. Of the TI-evaluable patients with baseline erythropoietin level less than 500 U/L and HTB, 38.5% (n=15/39) achieved TI for at least eight weeks over the first 24 weeks of treatment.

The FACIT-Fatigue scale, a measure of self-reported fatigue and its impact upon daily activities and function, was utilized to assess health-related quality of life, including in a subgroup of patients (n=17) achieving TI for at least 24 weeks over the first 48 weeks of treatment. Patients in this subgroup showed clinically meaningful improvements in QoL, and meaningful improvements in FACIT-Fatigue were observed early and generally continued to improve over time in patients with more durable TI responses.

The majority of patients enrolled in this ongoing trial had HTB and/or multi-lineage dysplasia, indicating a difficult-to-treat trial population. Durable TI responses continued to be observed in a broad range of patients with lower-risk MDS, including in those with HTB, which support the potential for elritercept to ameliorate ineffective hematopoiesis across multiple lineages in patients with MDS. These Phase 2 data further support the rationale for the planned Phase 3 RENEW registrational trial of elritercept in transfusion-dependent patients with very low-, low-, and intermediate risk MDS.

•Hematologic Improvement and Fatigue Reduction with Elritercept in Participants with Lower-Risk MDS with Non-Transfusion Dependent Anemia: New Analyses from an Ongoing Phase 2 Trial

In a subgroup analysis of patients that were non-transfused ("NT") at baseline, treatment with elritercept showed:

•Robust hematological responses observed with 93.3% (n=14/15) of NT patients having an increase greater than 1.0 g/dL and 86.7% (n=13/15) having an HI-E response.
•Durable HI-E responses observed with elritercept treatment with 100% (n=13/13) achieving a continuous response duration of greater than 24 weeks and 76.9% (n=10/13) achieving a cumulative response duration greater than 52 weeks.
•Sustained and durable increases in hemoglobin and soluble transferrin receptor, a marker of erythropoietic activity, were observed in NT participants.

•Overall improvement in mean platelet and neutrophil counts along with decreases in mean ferritin and hepcidin were observed after only one dose and were generally maintained through 48 weeks, demonstrating that elritercept has the potential to address ineffective hematopoiesis across multiple lineages and improve iron utilization and reduce inflammation.
•NT patients achieved meaningful improvements in FACIT-Fatigue scores, with improvements seen early, generally within the first two treatment cycles.

•Hematological Improvement and Other Clinical Benefits of Elrtiercept as Monotherapy and in Combination with Ruxolitinib in Participants with Myelofibrosis from the Ongoing Phase 2 RESTORE Trial

This ongoing, open-label, two-part Phase 2 clinical trial is evaluating elritercept administered with or without ruxolitinib in patients with MF who have anemia and were either currently on, failed, or ineligible for ruxolitinib at baseline. Safety data are presented for all patients that received at least one dose of elritercept (n=73) as of the August 30, 2024 data cutoff date. Evaluations of markers of hematopoiesis and anemia over 12 weeks, along with measurements of spleen volume and symptom scores (by the MF-symptom assessment form-Total Symptom Score, or "MF-SAF-TSS") over 24 weeks, were presented for dose levels 1 through 4 in Part 1 and the RP2D, ranging from 0.75 mg/kg to 5.0 mg/kg (collectively, the "efficacy evaluable patients"). Enrollment of Part 1 of the trial, the dose escalation portion, is complete. Part 2, the dose expansion portion, is open and enrolling with an RP2D of 3.75 mg/kg with the option to up-titrate to 5.0 mg/kg. All data presented from this trial is as of the data cutoff date.

Elritercept was generally well-tolerated by the safety population. There were six cases of fatal TEAEs in the trial that were each deemed unrelated to treatment. The most commonly reported TEAEs (in ≥15% of patients) were thrombocytopenia and diarrhea. The majority of treatment-related TEAEs were mild to moderate, with 12 patients experiencing Grade 3 or higher treatment-related TEAEs of thrombocytopenia. 93.3% (n=14/15) of patients with a TEAE of thrombocytopenia had baseline platelets below 150 x 109/L.

Additional data from the efficacy evaluable patients include:

•Increases in hemoglobin were observed in 82.8% (n=24/29) of evaluable non-transfusion dependent patients in both arms over a 12-week period within the first 24 weeks, suggesting that elritercept has the potential to address anemia due to MF and ruxolitinib-associated anemia.
•63.4% (n=26/41) of patients that received at least three RBC units per 12 weeks at baseline in both arms and all dose levels tested showed reductions in transfusion burden over 12 weeks within the first 24 weeks. 24.4% (n=10/41) of the patients who showed reductions in transfusion burdens achieved TI.
◦Additionally, within the subgroup of these patients in the combination arm who received a starting dose of 3.0 mg/kg of elritercept or higher, 62.5% (n=10/16) had reductions of 50% or greater, and 37.5% (n=6/16) achieved TI.
•At week 24, reduction in spleen volume was observed in 40% (n=8/20) of patients with baseline spleen size ≥ 450 cm3 and a week 24 spleen assessment, including three patients who had reductions of 35% or greater. Reductions in spleen volume in the combination arm generally occurred without an increase in ruxolitinib dose.
◦For evaluable patients in the combination arm with a starting dose of 3.0 mg/kg of elritercept or higher, 88% (n=7/8) had some reduction in spleen size at week 24
•At week 24, reduction in disease symptoms was observed in 66.7% (n=18/27) of patients with at least two symptoms with an average score ≥ 3 or an average total score of ≥ 10 on the MF-SAF-TSS questionnaire at baseline and a week 24 MF-SAF-TSS assessment. Five patients had reductions of at least 50%, including three in the monotherapy arm and two in the combination arm.

The data support the potential of elritercept to ameliorate ineffective hematopoiesis and address cytopenias due to MF and associated with ruxolitinib, and provide broader clinical benefit in patients, as supported by the observed reduction in spleen volume and improvement in total symptom scores.

About the Ongoing Phase 2 Clinical Trial of Elritercept in Patients with MDS (NCT04419649)

Keros is conducting an open label, two-part, multiple ascending dose Phase 2 clinical trial to evaluate elritercept in patients with very low-, low-, or intermediate-risk MDS who either have or have not previously received treatment with an erythroid stimulating agent.

The primary objective of this trial is to assess the safety and tolerability of elritercept in patients with MDS that are RS positive or non-RS. The primary objective of Part 2 of this trial is confirmation of the safety and tolerability of the RP2D (3.75 mg/kg and 5.0 mg/kg). The secondary objectives of this trial are to evaluate the pharmacokinetics, pharmacodynamics and efficacy of elritercept.

About the Ongoing Phase 2 Clinical Trial of Elritercept in Patients with MF-Associated Cytopenias (RESTORE trial; NCT05037760)

Keros is conducting an open label, two-part, multiple ascending dose Phase 2 clinical trial to evaluate elritercept as a monotherapy and in combination with ruxolitinib in patients with MF-associated cytopenias.

The primary objective of this trial is to assess the safety and tolerability of elritercept in patients with MF-associated cytopenias. The primary objective of Part 2 of this trial is confirmation of the safety and tolerability of the RP2D (3.75 mg/kg and 5.0 mg/kg). The secondary objectives of this trial are to evaluate the pharmacokinetics, pharmacodynamics and efficacy of elritercept administered with or without ruxolitinib.

About Elritercept

Elritercept is an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-ß receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. Elritercept is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with MF.

On December 09, 2024 Delta-Fly Pharma reported Following to the previous information on Oct. 28th. in 2024, we are excited to share our latest development status (Press release, Delta-Fly Pharma, DEC 9, 2024, View Source [SID1234648965]).

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We are pleased to announce that the data review committee (DMC) has approved the tolerability of the first three patients enrolled in the Phase I/II clinical trial of DFP-10917 in combination with Venetoclax (VEN) (NCT06382168) conducted at five US clinical sites for patients with acute myeloid leukemia (AML) who have failed/relapsed after standard VEN therapy (first-line therapy). Additionally, the bone marrow cell count in peripheral blood in all three cases was 0 (zero) within 4 (four) weeks of starting treatment, and complete remission (CR or CRi) was confirmed by subsequent bone marrow biopsy.

Three more patients will be added at the current dosage regimen, and after confirmation of the tolerability, the study will move to Phase II. Complete remission has been observed in patients who have failed/relapsed after existing VEN combination therapy (first-line therapy), so this is expected to be a new, highly effective second-line therapy for patients with AML.

As previously reported, the data cleaning processes for interim analysis are currently underway for Phase III comparative clinical trial (150 cases) of DFP-10917 monotherapy targeting patients with AML receiving third-line or later therapy. Once this is completed, the results will be submitted to the Independent Data Safety Monitoring Committee (DSMB) along with electrocardiogram and pharmacokinetic study results for their advice.

On December 9, 2024 GenScript Biotech, a global biotechnology leader in the life science, biologics manufacturing, synthetic biology, and cell therapies, and its partner, Base Therapeutics, reported the FDA approval of its NK510 program’s IND (Press release, GenScript, DEC 9, 2024, View Source [SID1234648964]). The NK510 cell program is an NK cell therapy for the clinical treatment of advanced solid tumors, and uses GenScript’s cGMP sgRNA to perform base editing, with CytoSinct Cell Isolation Nanobeads (GMP) and CytoSinct 1000 instruments to perform cell isolation. This is the first FDA IND approval of a base-edited NK cell program and follows NK510’s clinical trial approval by China’s NMPA in October 2024.

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"I am honored that Base Therapeutics has partnered with GenScript to advance the AccuBase Edited NK Cell Therapy project, NK510, which has successfully received IND approval in both the United States and China," remarked Dr. Tianhong Xu, founder of Base Therapeutics. "We are grateful to GenScript for providing services and products (sgRNA & instruments) that meet the regulatory requirements of both countries. This achievement not only marks a significant breakthrough in base editing technology, but also underscores our unwavering commitment to innovation, safety, and efficacy."

"GenScript congratulates Base Therapeutics on their remarkable achievements. We are proud to be the sole provider of their RUO to cGMP sgRNA material and cell isolation platform, essential for reliably generating accurately base-edited cells throughout the product development process," said Dr. Ray Chen, President of the Life Science Group at GenScript. "This collaboration underscores GenScript’s capabilities in supporting gene and cell therapy clients in achieving global IND approvals in an expedited timeline, ultimately helping them make innovative therapies more accessible worldwide."

NK510 is a universal "off-the-shelf" allogeneic NK cell program independently developed by Base Therapeutics. It leverages AccuBase, a proprietary zero off-target base editor with global freedom to operate (FTO) protection, to precisely modify key genes in NK cells, achieving over 90% editing efficiency.

GenScript’s GMP Guide RNA: Enabling Diversified Cell Therapies

With 22 years of expertise in nucleic acid synthesis, GenScript has built a comprehensive gene editing portfolio with RUO to cGMP grade materials, including chemically synthesized guide RNA (gRNA) and HDR knock-in templates. "We can produce cGMP gRNA up to 140 nucleotides long at gram-scale quantities, enabling a wide range of editing technologies, including Cas9, Cas12a, base editing, and prime editing," said Dr. Jianpeng Wang, Senior Director of GenScript’s GMP Production Department. "We also support the preparation of submission materials for regulatory agencies in the US, EU, and APAC markets. This combination of superior product quality and extensive regulatory experience makes GenScript an ideal partner for accelerating cell therapy development."

As of May 2024, GenScript has successfully delivered over 120 batches of cGMP gRNA and HDR knock-in templates, supported more than 40 regulatory submissions, passed over 30 audits, and helped global clients obtain 13 IND approvals.

GenScript’s CytoSinct Platform: Enabling Precise Nanobead-Based Cell Isolation

The CytoSinct Cell Isolation Nanobeads leverage advanced nanoparticle-empowered immuno-magnetic isolation technology to enrich specific cell populations of interest. Its expertise in antibody development and magnetic bead production ensures high precision and reliability. The CytoSinct 1000 Instrument complements the nanobead technology with automation for large scale processing and is designed with 21 CFR Part 11 compliance, adhering to FDA regulations for electronic records and e-signatures to safeguard data integrity throughout the cell isolation process. With customizable programming and alert functions streamline the operation, the system streamlines operations and ensures efficient and reliable automated cell isolation. The CytoSinct platform has also completed FDA DMF filing, underscoring its readiness for clinical applications.

On December 09, 2024 Daiichi Sankyo reported Datopotamab deruxtecan (Dato-DXd) has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR-mutated) non-small cell lung cancer (NSCLC) with disease progression on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (Press release, Daiichi Sankyo, DEC 9, 2024, View Source [SID1234648963]).

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Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat serious conditions and address significant unmet medical needs. The medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.

The FDA granted this BTD based on data from the TROPION-Lung05 phase 2 trial with supporting data from the TROPION-Lung01 phase 3 trial. Results from a pooled analysis of patients with previously treated EGFR-mutated NSCLC in these studies were presented this month at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia 2024 Congress. This is the first BTD for datopotamab deruxtecan and the twelfth BTD across Daiichi Sankyo’s oncology pipeline.

"The Breakthrough Therapy Designation granted by the FDA underscores the significant unmet need for new treatments for patients with previously treated EGFR-mutated non-small cell lung cancer who have experienced disease progression," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Datopotamab deruxtecan has the potential to play an important role in improving outcomes and we look forward to working closely with the FDA to bring this medicine to patients as quickly as possible."

"This Breakthrough Therapy Designation reinforces datopotamab deruxtecan as a promising potential therapy for patients with EGFR-mutated lung cancer who continue to face significant unmet needs following disease progression on or after initial treatments," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. "We are proud to have long supported patients with EGFR-mutated lung cancer and look forward to the possibility of bringing another innovative treatment option to this community."

Daiichi Sankyo and AstraZeneca recently announced the submission of a new Biologics License Application for accelerated approval in the U.S. for datopotamab deruxtecan for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior systemic therapies, including an EGFR-directed therapy.

About TROPION-Lung05
TROPION-Lung05 is a global, multicenter, single-arm, open-label phase 2 trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on at least one TKI (with or without other systemic therapies) and on or after one regimen of platinum-based chemotherapy. Patients receiving up to four prior lines of treatment with tumors with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial.

The primary trial endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary efficacy endpoints include duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety.

TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information visit ClinicalTrials.gov.

About TROPION-Lung01
TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

Primary PFS results and interim OS results from TROPION-Lung01 were presented at the 2023 ESMO (Free ESMO Whitepaper) (#ESMO23) Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology in September 2024.

About Advanced Non-Small Cell Lung Cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 80% of cases.2 Approximately 10% to 15% of patients with NSCLC in the U.S. and Europe, and 30% to 40% of patients in Asia have an EGFR mutation.3,4 The majority of EGFR mutations occur in tumors of nonsquamous histology.5

For patients with tumors that have an EGFR mutation, the established first-line treatment in the metastatic setting is an EGFR TKI.6 While EGFR TKIs have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive subsequent therapies, such as chemotherapy.7,8,9,10

TROP2 is a protein broadly expressed in the majority of NSCLC tumors.11 There is currently no TROP2 directed ADC approved for the treatment of lung cancer.6,12

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 low or negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.

About the DXd ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.