Oxaliplatin

On April 8, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single agent nivolumab for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC, that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan.Full prescribing information for Opdivo and Yervoy will be posted on Drugs@FDA.Efficacy and SafetyEfficacy of nivolumab with ipilimumab was evaluated in CHECKMATE-8HW (NCT04008030), a randomized, three-arm, open-label trial in immunotherapy-naïve patients with unresectable or metastatic CRC with known MSI-H or dMMR status. Patients were randomized to receive one of the following treatments:nivolumab 240 mg every 3 weeks and ipilimumab 1 mg/kg every 3 weeks for a maximum of 4 doses, then nivolumab 480 mg every 4 weeks,nivolumab 240 mg every 2 weeks for 6 doses, then nivolumab 480 mg every 4 weeks, orinvestigator’s choice chemotherapy:The major efficacy outcome measure was progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1 in patients with centrally confirmed MSI-H/dMMR status in the following pre-specified settings:First-line setting: nivolumab + ipilimumab versus chemotherapy,All lines: nivolumab + ipilimumab versus nivolumab alone.The analysis of nivolumab + ipilimumab versus chemotherapy in the first line setting was conducted in 255 patients with centrally confirmed MSI-H/dMMR status of 303 patients based on local testing. Median PFS was not reached (NR) (95% CI: 38.4, not estimable [NE]) in the nivolumab + ipilimumab arm and 5.8 months (95% CI: 4.4, 7.8) in the chemotherapy arm (Hazard ratio 0.21 [95% CI: 0.14, 0.32] p-value <0.0001). Comparative results of ORR and OS between arms were not available at the time of the interim PFS analysis due to statistical testing strategy.The analysis of nivolumab + ipilimumab versus nivolumab (all lines) was conducted in 582 patients with centrally confirmed MSI-H/dMMR status of 707 patients based on local testing. Median PFS was NR (95% CI: 53.8, NE) in the nivolumab + ipilimumab arm and 39.3 months (95% CI: 22.1, NE) in the nivolumab arm (Hazard ratio 0.62 [95% CI: 0.48, 0.81] p-value 0.0003). ORR was 71% (95% CI: 65, 76) in the nivolumab + ipilimumab arm and 58% (95% CI: 52, 63) in the nivolumab arm (p-value 0.0011). The comparative results of OS between arms were not available at the interim PFS analysis due to statistical testing strategy.The most common adverse reactions reported in ≥20% of patients treated with nivolumab with ipilimumab were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. The most common adverse reactions reported in ≥20% of patients treated with nivolumab as a single agent were fatigue, diarrhea, abdominal pain, pruritis, and musculoskeletal pain.See the prescribing information for the recommended doses of nivolumab and ipilimumab.Expedited ProgramsThis review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency (ANVISA), the Israel Ministry of Health (IMoH), and Health Canada (HC). The application reviews are ongoing at the other regulatory agencies.This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 10 weeks ahead of the FDA goal date.This application was granted priority review, breakthrough designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.

TOKYO, Japan & BASKING RIDGE, NJ, USA I March 31, 2025 I The first patient has been dosed in the DESTINY-Gastric05 phase 3 trial evaluating ENHERTU ® (trastuzumab deruxtecan) in combination with a fluoropyrimidine chemotherapy (5-FU or capecitabine) and Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy KEYTRUDA ® (pembrolizumab) versus trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab in previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) cancer with PD-L1 CPS ≥1. An exploratory cohort of patients with PD-L1 CPS <1 will be randomized to either ENHERTU plus fluoropyrimidine or trastuzumab plus platinum-based chemotherapy. ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 1 Current recommended first-line treatment for HER2 positive advanced gastric cancer with PD-L1 CPS ≥1 is trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab. 2,3 New treatment strategies are needed to continue to improve survival, including additional HER2 directed treatment options. “Following the positive overall survival results seen with DESTINY-Gastric04 in the second-line HER2 positive metastatic gastric cancer setting, the DESTINY-Gastric05 trial will explore the role of ENHERTU earlier in the metastatic setting as a first-line treatment,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “With DESTINY-Gastric05, we are evaluating whether a potential platinum-free chemotherapy regimen of ENHERTU combined with immunotherapy and a fluoropyrimidine chemotherapy can further improve survival in patients with previously untreated HER2 positive metastatic gastric cancer.” ENHERTU is currently approved in more than 65 countries in the second-line or third-line metastatic setting of HER2 positive gastric cancer based on DESTINY-Gastric01 , a randomized phase 2 trial, and DESTINY-Gastric02 and DESTINY-Gastric06 , two single-arm phase 2 trials. KEYTRUDA ® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About DESTINY-Gastric05 DESTINY-Gastric05 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with a fluoropyrimidine-based chemotherapy (5-FU or capecitabine) and Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy KEYTRUDA ® (pembrolizumab) versus trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab in approximately 576 previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or GEJ cancer with PD-L1 CPS ≥1. The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review. The key secondary endpoint is overall survival. Additional secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response and safety. An exploratory cohort of 150 patients with PD-L1 CPS <1 will be randomized to either ENHERTU plus fluoropyrimidine (5-FU or capecitabine) or trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine). DESTINY-Gastric05 will enroll patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov . About HER2 Positive Gastric Cancer Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death. 4 Approximately one million cases were diagnosed in 2022. 4 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 1 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer. 5 Approximately one in five gastric cancers globally are HER2 positive. 5,6 Recommended first-line treatment for HER2 positive advanced gastric cancer with PD-L1 CPS ≥1 is trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab. 2,3 In patients with PD-L1 CPS <1 recommended first-line treatment is trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine). 2 New treatment strategies, including additional HER2 directed treatment options, are needed to continue to improve survival in patients with previously untreated advanced gastric cancer. 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 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [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 75 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 the U.S. for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4 mg/kg) is approved in more than 50 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 and/or DESTINY-Lung05 trials. Continued approval in China and 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 65 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 adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (5.4 mg/kg) is approved in Brazil, Israel, Russia and 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 may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the ENHERTU Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway. 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 DATROWAY ® 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 DATROWAY. About the 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 DATROWAY, 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. 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. Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 Casamayor M, et al. Ecancermedicalscience .2018;12:883. 2 NCCN Clinical Practice Guidelines. Gastric Cancer . V.1.2025. Accessed March 2025. 3 ESMO. Gastric Cancer Living Guidelines , v 33.10. October 2022. Accessed March 2025. 4 Globocan 2022. Stomach Cancer . Accessed March 2025. 5 Abrahao-Machado LF, et al. World J Gastroenterol . 2016;22(19):4619-25. 6 Iqbal N, et al. Mol Biol Int . 2014:852748. SOURCE: Daiichi Sankyo