Ifinatamab Deruxtecan for Cancer

Recruiting at 193 trial locations

Overseen By (Asia) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Daiichi Sankyo

Must not be taking: Steroids, Anticonvulsants

Disqualifiers: Brain metastases, Spinal cord compression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 22

Duration: Up to 57 months

520 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is exploring ifinatamab deruxtecan (I-DXD), an experimental treatment, to assess its efficacy and safety for various cancers, including endometrial, head and neck, pancreatic, and colorectal. The trial targets individuals whose cancers have recurred or spread after previous treatments. Participants typically need a measurable tumor that can be biopsied, and their cancer must have worsened following earlier treatments. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions an 'inadequate treatment washout period' as a disqualification criterion, suggesting that some medications might need to be paused before joining the study. It's best to discuss this with the trial coordinators.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that ifinatamab deruxtecan (I-DXd) generally has a manageable safety profile in patients with advanced solid tumors. The safety results align with earlier findings. Some side effects have occurred, but they are typical for cancer treatments.

In one study involving patients with advanced solid tumors, such as endometrial, pancreatic, and colorectal cancers, I-DXd was well-tolerated. Side effects were reported but were manageable and similar to those seen with other cancer treatments.

While detailed safety information for each specific cancer type in the trial isn't available, the overall results suggest that I-DXd is tolerable. This makes it a promising option for those considering joining a trial. However, discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Researchers are excited about Ifinatamab Deruxtecan because it represents a novel approach to treating various types of cancer. Unlike traditional chemotherapy, which broadly attacks fast-growing cells, Ifinatamab Deruxtecan is an antibody-drug conjugate specifically designed to target and deliver chemotherapy directly to cancer cells, potentially reducing damage to healthy cells. This precision targeting could lead to more effective treatments with fewer side effects. Additionally, Ifinatamab Deruxtecan is being explored across a wide range of cancers, including some with limited treatment options, offering hope for patients with recurrent or metastatic conditions.

What evidence suggests that this trial's treatments could be effective?

Research has shown that ifinatamab deruxtecan (I-DXd) holds promise for treating several types of cancer. In this trial, participants with various recurrent or metastatic cancers, such as head and neck cancer, colorectal cancer, and biliary tract cancer, will receive I-DXd. Specifically, studies found that in head and neck cancer, 52.4% of previously treated patients experienced tumor shrinkage, meaning more than half saw their tumors get smaller. For colorectal cancer, I-DXd yielded positive results, with some patients remaining on treatment for months, suggesting its potential effectiveness. In biliary tract cancer, I-DXd demonstrated its ability to fight tumors effectively and is generally safe. Across different cancers, I-DXd has acted quickly, and its effects have lasted. While more research is needed, these findings suggest I-DXd could be a helpful treatment for certain cancers. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain types of advanced or metastatic solid tumors that have worsened after previous treatments. Participants need to have a measurable tumor, be able to provide tissue samples, and must not have serious health issues affecting their organs. Women who can bear children and men must agree to use effective contraception.

Inclusion Criteria

Sign and date the informed consent form prior to the start of any study-specific qualification procedures.

My liver is functioning well.

My organs are functioning well enough for the study drug.

Exclusion Criteria

I have had a transplant of bone marrow, stem cells, or an organ.

History of hypersensitivity to the drug substances, inactive ingredients in the drug product, or severe hypersensitivity reactions to other monoclonal antibodies.

Has an active, known, or suspected autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

HCC Safety Run-In (Phase 1)

Assess the safety and tolerability of I-DXd in participants with hepatocellular carcinoma

3 weeks

Cycle 1 Day 1 to Cycle 1 Day 21

Treatment

Participants receive intravenous infusion of I-DXd at the determined dose

Up to 57 months

Every 21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

47 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• Ifinatamab Deruxtecan

Trial Overview The study tests Ifinatamab Deruxtecan (I-DXD) on various solid tumors including cancers of the endometrium, head & neck, pancreas, colon & rectum, liver, esophagus/stomach junction & stomach itself, lung (non-squamous), and urinary system.

How Is the Trial Designed?

Group I: Cohort 9: Cervical cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic cervical cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group II: Cohort 8: Ovarian cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic non-squamous ovarian cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group III: Cohort 7: Urothelial carcinoma Experimental Treatment 1 Intervention

Participants with recurrent or metastatic urothelial carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group IV: Cohort 6: Adenocarcinoma of esophagus, gastroesophageal junction, and stomach Experimental Treatment 1 Intervention

Participants with recurrent or metastatic adenocarcinoma of esophagus, gastroesophageal junction, and stomach who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group V: Cohort 5: Hepatocellular Carcinoma Experimental Treatment 1 Intervention

Participants with recurrent or metastatic hepatocellular carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd at the determined dose.

Group VI: Cohort 4: Colorectal Cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic colorectal cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group VII: Cohort 3: Pancreatic Ductal Adenocarcinoma Experimental Treatment 1 Intervention

Participants with recurrent or metastatic pancreatic ductal adenocarcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group VIII: Cohort 2: Head and Neck Squamous Cell Carcinoma Experimental Treatment 1 Intervention

Participants with recurrent or metastatic head and neck squamous carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group IX: Cohort 1: Endometrial Cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic endometrial cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group X: Cohort 13: Cutaneous melanoma Experimental Treatment 1 Intervention

Participants with recurrent or metastatic cutaneous melanoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group XI: Cohort 12: HER2 immunohistochemistry (IHC) 0 breast cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic HER2 immunohistochemistry (IHC) 0 breast cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group XII: Cohort 11: Human epidermal growth factor 2 (HER2)-low breast cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic human epidermal growth factor 2 (HER2)-low breast cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Group XIII: Cohort 10: Biliary tract cancer Experimental Treatment 1 Intervention

Participants with recurrent or metastatic biliary tract cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In the TUXEDO-1 trial involving 15 patients with HER2-positive breast cancer and brain metastases, trastuzumab deruxtecan achieved a high overall intracranial response rate of 73.3%, indicating its efficacy in treating this challenging condition.

The treatment was well-tolerated, with no new safety concerns reported, and patients maintained their quality of life and cognitive functioning throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Bartsch, R., Berghoff, AS., Furtner, J., et al.[2022]

Trastuzumab deruxtecan (T-DXd) showed promising antitumor activity in patients with advanced HER2-low breast cancer, achieving a 37% objective response rate in a study of 54 patients who had undergone a median of 7.5 prior therapies.

While T-DXd demonstrated efficacy, it also presented significant safety concerns, with 98% of patients experiencing treatment-emergent adverse events, including severe cases of interstitial lung disease (ILD) that led to fatalities, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Modi, S., Park, H., Murthy, RK., et al.[2021]

Trastuzumab deruxtecan (T-DXd) was evaluated for safety in 1457 patients across 8 clinical trials, revealing that gastrointestinal disorders and blood-related issues were the most common adverse events, with neutropenia being the most severe (21.4% incidence).

The study highlighted significant concerns regarding interstitial lung disease (10.9% incidence) and decreased left ventricular ejection fraction (1.2% incidence), suggesting that while T-DXd is generally well tolerated, these specific side effects require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. Guo, Z., Ding, Y., Wang, M., et al.[2023]

Trastuzumab-deruxtecan (T-DXd) is a promising antibody-drug conjugate that shows clinically relevant activity in heavily pretreated patients with HER2-positive metastatic breast cancer, particularly those who have progressed on T-DM1.

While T-DXd demonstrates efficacy, it is important to monitor for interstitial lung disease, which occurred in about 13% of patients, highlighting the need for careful patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer. Bartsch, R.[2022]

In the phase 3 DESTINY-Breast02 trial involving 608 patients with HER2-positive metastatic breast cancer, trastuzumab deruxtecan significantly improved median progression-free survival to 17.8 months compared to 6.9 months for treatment of physician's choice, demonstrating its efficacy in a population with limited treatment options.

While trastuzumab deruxtecan had a higher incidence of treatment-emergent adverse events, including nausea and interstitial lung disease, it still showed a favorable benefit-risk profile, indicating its potential as a viable treatment option for patients resistant to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. André, F., Hee Park, Y., Kim, SB., et al.[2023]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

In a comparison of the safety profiles of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) using data from 3723 and 2045 adverse event reports respectively, T-DXd was associated with higher rates of fatal outcomes in the hematologic and respiratory systems, while T-DM1 had more severe outcomes in the hepatobiliary system.

Both drugs showed distinct adverse event patterns, with T-DM1 linked to nervous and musculoskeletal issues, and T-DXd associated with respiratory and gastrointestinal problems, highlighting the need for careful monitoring of specific risks in patients, especially those over 65 or on certain drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. Liu, F., Yin, G., Xue, S., et al.[2023]

In an expanded-access study involving 64 patients with HER2-positive gastric or gastroesophageal junction adenocarcinomas, trastuzumab deruxtecan (T-DXd) was administered safely, with no new safety concerns identified prior to its marketing approval in Japan.

Serious adverse events (SAEs) were reported in 26.6% of patients, with febrile neutropenia being the most common; however, drug-related SAEs led to death in only one patient, indicating a manageable safety profile for T-DXd.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study. Shitara, K., Yamaguchi, K., Muro, K., et al.[2023]

Trastuzumab deruxtecan (T-DXd) demonstrated clinical activity in patients with HER2-low gastric or gastroesophageal junction adenocarcinoma, showing a confirmed objective response rate of 26.3% in cohort 1 and 9.5% in cohort 2, with many patients experiencing reduced tumor size.

The treatment was generally well-tolerated, with no drug-related deaths reported, although some patients experienced significant adverse events like anemia and decreased neutrophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. Yamaguchi, K., Bang, YJ., Iwasa, S., et al.[2023]

In a phase 1 trial involving 24 patients with advanced breast and gastric cancers, trastuzumab deruxtecan demonstrated promising antitumor activity, achieving a 43% objective response rate and 91% disease control rate, even in patients with low HER2 expression.

The study found that trastuzumab deruxtecan was well-tolerated, with no dose-limiting toxicities or significant cardiovascular effects reported, suggesting a maximum tolerated dose was not reached and indicating a favorable safety profile for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Doi, T., Shitara, K., Naito, Y., et al.[2018]

In a phase I trial, datopotamab deruxtecan showed promising response rates, with 34% of patients with advanced or metastatic triple-negative breast cancer experiencing a complete or partial response.

The treatment was found to have manageable toxicity, indicating it may be a safe option for patients who have not responded to multiple previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Very Compelling" Results for ADC in TNBC Trial. [2022]

In a phase 1 trial involving 115 patients with HER2-positive breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a manageable safety profile, with 59.5% of patients achieving a confirmed objective response.

Despite some serious treatment-emergent adverse events, including cases of interstitial lung disease and pneumonitis, the preliminary efficacy results suggest that trastuzumab deruxtecan is a promising treatment option, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Tamura, K., Tsurutani, J., Takahashi, S., et al.[2020]

Citations

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First Patient Dosed in Study of I-DXd in Esophageal Cancer “Patients with metastatic esophageal squamous cell carcinoma continue to experience poor outcomes despite currently available treatments,” said ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06330064

NCT06330064 | A Study To Evaluate The Efficacy And ... This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXD) in the following tumor types: endometrial cancer (EC); head and ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00431

A Study To Evaluate The Efficacy And Safety Of Ifinatamab ... This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXD) in the following tumor types: endometrial cancer (EC); head and neck ...

4. daiichisankyo.us daiichisankyo.us/press-releases/-/article/ideate-esophageal01-phase-3-trial-of-ifinatamab-deruxtecan-initiated-in-certain-patients-with-pretreated-advanced-or-metastatic-esophageal-squamous-cell-carcinoma

IDeate-Esophageal01 Phase 3 Trial of Ifinatamab ... ESCC accounts for nearly 90% of esophageal cancers globally with a five-year overall survival rate around 15% to 20% and has a worse prognosis ...

5. merck.com merck.com/news/ideate-esophageal01-phase-3-trial-of-ifinatamab-deruxtecan-initiated-in-certain-patients-with-pretreated-advanced-or-metastatic-esophageal-squamous-cell-carcinoma/

IDeate-Esophageal01 Phase 3 Trial of Ifinatamab ... ESCC accounts for nearly 90% of esophageal cancers globally with a five-year overall survival rate around 15% to 20% and has a worse prognosis ...

6. daiichisankyo.us daiichisankyo.us/press-releases/-/article/daiichi-sankyo-continues-to-transform-standards-of-care-for-patients-with-three-landmark-breast-cancer-trials-and-additional-data-across-industry-leading-adc-portfolio-at-esmo

Press Releases Trastuzumab deruxtecan (T-DXd) in patients with HER2+ gastric cancer or gastroesophageal junction adenocarcinoma who received prior anti ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3157

IDeate-PanTumor02: A phase 1b/2 study to evaluate the ... We describe a study investigating the efficacy and safety of I-DXd in pts with advanced solid tumors with substantial unmet medical needs.