- Goal response price of 54.8% seen with Daiichi Sankyo and Merck’s ifinatamab deruxtecan at 12 mg/kg dose in pretreated sufferers
- 12 mg/kg chosen as optimum dose for extension a part of IDeate-Lung01 part 2 trial and lately initiated IDeate-Lung02 part 3 examine
BASKING RIDGE, N.J. & RAHWAY, N.J.–(BUSINESS WIRE)–Outcomes from an interim evaluation of the dose-optimization a part of the continuing IDeate-Lung01 part 2 trial confirmed ifinatamab deruxtecan (I-DXd) continues to exhibit promising goal response charges in sufferers with pretreated extensive-stage small cell lung most cancers (ES-SCLC). These information had been featured at the moment as a part of a press convention and might be introduced throughout an oral presentation (OA04.03) on Sunday on the 2024 World Convention on Lung Most cancers (#WCLC24) hosted by the Worldwide Affiliation for the Examine of Lung Most cancers.
Ifinatamab deruxtecan is a particularly engineered, potential first-in-class B7-H3 directed antibody drug conjugate (ADC) found by Daiichi Sankyo (TSE: 4568) and being collectively developed by Daiichi Sankyo and Merck (NYSE: MRK), referred to as MSD outdoors of the USA and Canada.
Small cell lung most cancers (SCLC) is the second most typical kind of lung most cancers, accounting for about 15% of instances.1 SCLC is aggressive and progresses quickly to the metastatic stage, which has a five-year survival price of solely 3%.2,3 Roughly 65% of all SCLC tumors have a moderate-to-high expression of the protein B7-H3, which is related to illness development and poor prognosis.4,5
Most sufferers handled for small cell lung most cancers expertise speedy development of illness and there’s a excessive unmet want within the superior setting, stated Charles M. Rudin, MD, PhD, Deputy Director of Memorial Sloan Kettering Most cancers Heart and Co-Director of the Fiona and Stanley Druckenmiller Heart for Lung Most cancers Analysis. These interim outcomes from the primary a part of the IDeate-Lung01 trial recommend that ifinatamab deruxtecan may play an vital position in treating sufferers with pretreated extensive-stage small cell lung most cancers and additional analysis is warranted.
A confirmed goal response price (ORR) of 54.8% (95% CI: 38.7-70.2) and 26.1% (95% CI: 14.3-41.1) had been noticed in sufferers with ES-SCLC receiving ifinatamab deruxtecan within the 12 mg/kg (n=42) and eight mg/kg (n=46) cohorts, respectively, as assessed by blinded impartial central overview (BICR). Twenty-three partial responses (PR) had been seen within the 12 mg/kg cohort. One full response (CR) and eleven PRs had been seen within the 8 mg/kg cohort. A median length of response (DoR) of 4.2 months (95% CI: 3.5-7.0) and seven.9 months (95% CI: 4.1-NE) and a illness management price (DCR) of 90.5% (95% CI: 77.4-97.3) and 80.4% (95% CI: 66.1-90.6) had been noticed within the 12 mg/kg and eight mg/kg cohorts, respectively. The median length of remedy was 4.7 months for the 12 mg/kg dose (vary, 0.03-15.2) and three.5 months for the 8 mg/kg dose (vary, 0.03“13.9). Median progression-free survival (PFS) of 5.5 months (95% CI: 4.2-6.7) and 4.2 months (95% CI: 2.8-5.6) and median general survival (OS) of 11.8 months (95% CI: 8.9-15.3) and 9.4 months (95% CI: 7.8-15.9) had been noticed within the 12 mg/kg and eight mg/kg cohorts, respectively. The 12 mg/kg dose has been chosen for the dose growth a part of the trial. Median follow-up was 15.3 months (95% CI: 13.6-16.2) within the 12 mg/kg cohort and 14.6 months (95% CI: 13.4-16.5) within the 8 mg/kg cohort as of knowledge cutoff of April 25, 2024.
In a subset of sufferers with mind goal lesions at baseline, an intracranial ORR of fifty.0% (95% CI: 18.7-81.3) and 66.7% (95% CI: 22.3-95.7) had been noticed as assessed by central nervous system (CNS) BICR within the 12 mg/kg (n=10) and eight mg/kg (n=6) cohorts, respectively. In these sufferers, two intracranial CRs had been seen in every cohort. Three and two intracranial PRs and 5 and two instances of steady illness (SD) had been seen within the 12 mg/kg and eight mg/kg cohorts, respectively.
The target response price and median general survival of almost a yr together with the preliminary intracranial responses noticed reinforces the potential for ifinatamab deruxtecan to enhance outcomes for sufferers residing with this difficult-to-treat kind of lung most cancers, stated Mark Rutstein, MD, World Head, Oncology Medical Improvement, Daiichi Sankyo. We stay up for seeing further outcomes from the extension a part of the IDeate-Lung01 part 2 trial and the lately initiated IDeate-Lung02 part 3 trial the place we’re evaluating ifinatamab deruxtecan in sufferers with extensive-stage small cell lung most cancers versus remedy of doctor’s selection of chemotherapy.
These outcomes exhibit promising goal response charges in sufferers with pre-treated extensive-stage small cell lung most cancers, a affected person inhabitants with a poor prognosis and restricted remedy choices, stated Marjorie Inexperienced, MD, Senior Vice President and Head of Oncology, World Medical Improvement, Merck Analysis Laboratories. We’re inspired by these outcomes supporting the potential of B7-H3 as an actionable goal in small cell lung most cancers and stay up for advancing our pivotal scientific growth program for ifinatamab deruxtecan.
The security profile seen in IDeate-Lung01 is in line with that noticed for ifinatamab deruxtecan in earlier trials with no new security indicators recognized. Grade 3 or increased treatment-emergent adversarial occasions (TEAEs) occurred in 50.0% and 43.5% of sufferers within the 12 mg/kg (n=42) and eight mg/kg (n=46) cohorts, respectively. The commonest treatment-related TEAEs (>20% of complete inhabitants) throughout each doses embody nausea (50.0% and 28.3%), decreased urge for food (42.9% and 17.4%), anemia (35.7% and 13.0%), decreased neutrophil depend/neutropenia (33.3% and 10.9%), white blood cell decreased (21.4% and 4.3%) and asthenia (1.4% and 13.0%). 5 (11.9%) and 4 (8.7%) interstitial lung illness (ILD)/pneumonitis occasions had been confirmed as treatment-related within the 12 mg/kg and eight mg/kg doses, respectively, as decided by an impartial adjudication committee. Nearly all of ILD occasions (4 with 12 mg/kg, three with 8 mg/kg) had been low grade (grade 1 or 2). There was one grade 3 (12 mg/kg) and one grade 5 (8 mg/kg) ILD. No ILD occasions had been pending adjudication on the time of knowledge cutoff of April 25, 2024. Remedy discontinuations on account of adversarial occasions occurred in 16.7% and 6.5% within the 12 mg/kg and eight mg/kg cohorts, respectively.
Sufferers in IDeate-Lung01 receiving ifinatamab deruxtecan acquired a median of two traces of remedy in each dose teams together with a majority (76.1%) beforehand handled with immunotherapy. The median remedy length was 4.7 months (vary: 0.03-15.2) within the 12 mg/kg cohort and three.5 months (vary: 0.03-13.9) within the 8mg/kg cohort.
Abstract of IDeate-Lung01 Outcomes
|
Efficacy Measure |
Ifinatamab deruxtecan (12 mg/kg) n=42 |
Ifinatamab deruxtecan (8 mg/kg) n=46 |
|
Confirmed ORR, % (95% CI) |
54.8% (38.7-70.2) |
26.1% (14.3-41.1) |
|
CR, n (%) |
0 |
1 (2.2%) |
|
PR, n (%) |
23 (54.8%) |
11 (23.9%) |
|
Secure illness (SD)/non-CR/non-PD, n (%) |
15 (35.7%) |
25 (54.3%) |
|
Progressive illness (PD), n (%) |
2 (4.8%) |
5 (10.9%) |
|
DCR, % (95% CI) |
90.5% (77.4-97.3) |
80.4% (66.1-90.6) |
|
DoR, median (95% CI), months |
4.2 months (3.5-7.0) |
7.9 months (4.1-NE) |
|
TTR, median (95% CI), months |
1.4 months (1.0-8.1) |
1.4 months (1.2-1.5) |
|
PFS, median (95% CI), months |
5.5 months (4.2-6.7) |
4.2 months (2.8-5.6) |
|
OS, median (95% CI), months |
11.8 months (8.9-15.3) |
9.4 months (7.8-15.9) |
CR, full response; DCR, illness management price; DoR, length of response; ORR, goal response price; OS, general survival, PR, partial response; PD, progressive illness; PFS, progression-free survival; TTR, time to response; SD, steady illness
In regards to the IDeate-Lung01 Trial
IDeate-Lung01 is a world, multicenter, randomized, open-label two-part part 2 trial evaluating the protection and efficacy of ifinatamab deruxtecan in sufferers with ES-SCLC. Within the first a part of the trial (dose optimization), sufferers had been beforehand handled with at the very least one prior line of platinum-based chemotherapy and a most of three prior traces of remedy. Within the second half (extension), sufferers had been beforehand handled with a minimal of two earlier traces of systemic remedy.
Within the first a part of the trial, sufferers had been randomized 1:1 to obtain both 8 mg/kg or 12 mg/kg of ifinatamab deruxtecan. Within the second a part of the trial, sufferers will obtain the really helpful dose for growth (12 mg/kg) of ifinatamab deruxtecan.
The first endpoint is ORR as assessed by BICR. Secondary endpoints embody DoR, PFS, OS, DCR, time to response and general security profile. Intracranial ORR was assessed by BICR as an exploratory evaluation.
IDeate-Lung01 is enrolling sufferers in Asia, Europe and North America. For extra details about the trial, go to ClinicalTrials.gov.
About Small Cell Lung Most cancers
Greater than 2.48 million lung most cancers instances had been identified globally in 2022.6 SCLC is the second most typical kind of lung most cancers, accounting for roughly 15% of instances.1 SCLC is aggressive and progresses quickly to the metastatic stage, which has a five-year survival price of solely 3%.2,3 Whereas standard first-line remedy for sufferers with superior SCLC could assist some sufferers dwell longer, the present second-line customary of care affords restricted scientific profit and new remedy approaches are wanted.7,8,9,10
About B7-H3
B7-H3 is a transmembrane protein that belongs to the B7 household of proteins which bind to the CD28 household of receptors that features PD-1.11,12 B7-H3 is overexpressed in a variety of most cancers varieties, together with SCLC, and its overexpression has been proven to correlate with poor prognosis, making B7-H3 a promising therapeutic goal.4,12,13,14,15 There are at the moment no B7-H3 directed medicines permitted for the remedy of any most cancers.
About Ifinatamab Deruxtecan
Ifinatamab deruxtecan (I-DXd) is an investigational potential first-in-class B7-H3 directed ADC. Designed utilizing Daiichi Sankyo’s proprietary DXd ADC Know-how, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody hooked up to a variety of topoisomerase I inhibitor payloads (an exatecan spinoff, DXd) by way of tetrapeptide-based cleavable linkers.
Ifinatamab deruxtecan is being evaluated in a world growth program, which incorporates IDeate-Lung01, a part 2 monotherapy trial in sufferers with beforehand handled ES-SCLC; IDeate-Lung02, a part 3 trial in sufferers with relapsed SCLC versus investigator’s selection of chemotherapy; IDeate-Lung03, a part 1b/2 trial in sufferers with ES-SCLC together with atezolizumab with or with out carboplatin as first-line induction or upkeep remedy; IDeate-PanTumor01, a part 1/2 first-in-human trial in sufferers with superior strong malignant tumors in collaboration with Sarah Cannon Analysis Institute (SCRI) with examine operational oversight and supply offered via SCRI’s early part oncology scientific analysis group, SCRI Improvement Improvements in Nashville, TN; and, IDeate-PanTumor02, a part 2 trial in sufferers with recurrent or metastatic strong tumors.
Ifinatamab deruxtecan was granted orphan drug designation by the U.S. Meals and Drug Administration in April 2023 and by the European Fee in February 2024 for the remedy of SCLC.
In regards to the Daiichi Sankyo and Merck Collaboration
Daiichi Sankyo and Merck entered into a world collaboration in October 2023 to collectively develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), besides in Japan the place Daiichi Sankyo will preserve unique rights. Daiichi Sankyo might be solely answerable for manufacturing and provide. In August 2024, the worldwide co-development and co-commercialization settlement was expanded to incorporate MK-6070, an investigational delta-like ligand 3 (DLL3) concentrating on T-cell engager, which they are going to collectively develop and commercialize worldwide, besides in Japan the place Merck will preserve unique rights. Merck might be solely answerable for manufacturing and provide for MK-6070.
In regards to the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in scientific growth crafted from two distinct ADC know-how platforms found in-house by Daiichi Sankyo.
The ADC platform furthest in scientific growth is Daiichi Sankyo’s DXd ADC Know-how the place every ADC consists of a monoclonal antibody hooked up to a variety of topoisomerase I inhibitor payloads (an exatecan spinoff, DXd) by way of tetrapeptide-based cleavable linkers. The DXd ADC portfolio at the moment consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, that are being collectively developed and commercialized globally with AstraZeneca (NASDAQ:). 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 collectively developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.
The second Daiichi Sankyo ADC platform consists of a monoclonal antibody hooked up to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the primary of a number of deliberate ADCs in scientific growth using this platform.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that haven’t been permitted for any indication in any nation. Security and efficacy haven’t been established.
About Daiichi Sankyo
Daiichi Sankyo is an progressive international healthcare firm contributing to the sustainable growth of society that discovers, develops and delivers new requirements of care to complement the standard of life all over the world. With greater than 120 years of expertise, Daiichi Sankyo leverages its world-class science and know-how to create new modalities and progressive medicines for folks with most cancers, cardiovascular and different ailments with excessive unmet medical wants. For extra info, please go to www.daiichisankyo.com.
Merck’s Give attention to Most cancers
Every single day, we observe the science as we work to find improvements that may assist sufferers, it doesn’t matter what stage of most cancers they’ve. As a number one oncology firm, we’re pursuing analysis the place scientific alternative and medical want converge, underpinned by our various pipeline of greater than 25 novel mechanisms. With one of many largest scientific growth packages throughout greater than 30 tumor varieties, we try to advance breakthrough science that may form the way forward for oncology. By addressing limitations to scientific trial participation, screening and remedy, we work with urgency to cut back disparities and assist guarantee sufferers have entry to high-quality most cancers care. Our unwavering dedication is what’s going to carry us nearer to our aim of bringing life to extra sufferers with most cancers. For extra info, go to https://www.merck.com/analysis/oncology/.
About Merck
At Merck, referred to as MSD outdoors of the USA and Canada, we’re unified round our function: We use the facility of modern science to avoid wasting and enhance lives all over the world. For greater than 130 years, we’ve introduced hope to humanity via the event of vital medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical firm on the earth “ and at the moment, we’re on the forefront of analysis to ship progressive well being options that advance the prevention and remedy of ailments in folks and animals. We foster a various and inclusive international workforce and function responsibly day-after-day to allow a secure, sustainable and wholesome future for all folks and communities. For extra info, go to www.merck.com and join with us on X (previously Twitter), Fb (NASDAQ:), Instagram, YouTube and LinkedIn.
Ahead-Wanting Assertion of Merck & Co., Inc., Rahway, N.J., USA
This information launch of Merck & Co., Inc., Rahway, N.J., USA (the corporate) consists of forward-looking statements throughout the that means of the secure harbor provisions of the U.S. Personal Securities Litigation Reform Act of 1995. These statements are based mostly upon the present beliefs and expectations of the corporate’s administration and are topic to vital dangers and uncertainties. There could be no ensures with respect to pipeline candidates that the candidates will obtain the required regulatory approvals or that they are going to show to be commercially profitable. If underlying assumptions show inaccurate or dangers or uncertainties materialize, precise outcomes could differ materially from these set forth within the forward-looking statements.
Dangers and uncertainties embody however usually are not restricted to, normal business circumstances and competitors; normal financial elements, together with rate of interest and foreign money trade price fluctuations; the impression of pharmaceutical business regulation and well being care laws in the USA and internationally; international tendencies towards well being care price containment; technological advances, new merchandise and patents attained by rivals; challenges inherent in new product growth, together with acquiring regulatory approval; the corporate’s skill to precisely predict future market circumstances; manufacturing difficulties or delays; monetary instability of worldwide economies and sovereign threat; dependence on the effectiveness of the corporate’s patents and different protections for progressive merchandise; and the publicity to litigation, together with patent litigation, and/or regulatory actions.
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References:
1 Schabath MB, et al. Most cancers Epidemiol Biomarkers Prev. 2019 Oct;28(10):1563-1579.
2 Rudin CM, et al. Nat Rev Dis Primers. 2021;7(1):3.
3 Most cancers.web. Lung Most cancers – Small Cell: Statistics. Accessed August 2024.
4 Qiu M-j, et al. Entrance. Oncol. 2021;11:600238.
5 Dong P, et al. Entrance Oncol. 2018;8:264
6 World Well being Group. Worldwide Company for Analysis on Most cancers. U.S. Most cancers Truth Sheet. Accessed August 2024.
7 American Most cancers Society. Remedy Decisions for Small Cell Lung Most cancers, by Stage. Accessed August 2024.
8 Liu SV, et al. J Clin Oncol. 2021;39(6):619-30.
9 Paz-Ares L, et al. ESMO Open. 2022;7(2):100408.
10 von Pawel J, et al. J Clin Oncol. 2014; 32:4012-4019.
11 Zhao B, et al. J Hematol Oncol. 2022;15(1):153.
12 Janakiram M, et al. Immunol Rev. 2017;276(1):26-39.
13 Picarda E, et al. Clin Most cancers Res. 2016;22(14):3425-3431.
14 Bendell JC, et al. J Clin Oncol. 2020;39(15 suppl 1). Summary TPS3646.
15 Kontos F, et al. Clin Most cancers Res. 2021;27(5):1227-1235.
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