I-DXd for Advanced Cancer

Recruiting at 21 trial locations

Overseen By (Japan sites) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Daiichi Sankyo

Disqualifiers: Multiple malignancies, Cardiovascular disease, Pulmonary compromise, others

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

Compensation: Varies

Number of Visits: 6

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new drug, ifinatamab deruxtecan (I-DXd), for individuals with advanced solid tumors unresponsive to other treatments. The study will first determine the safest dose and then evaluate the drug's effectiveness on its own. Participants may qualify if they have specific types of cancer, such as certain lung, breast, or bladder cancers, that have not responded to standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires an adequate treatment washout period (time without taking certain medications) before starting the study treatment, which means you may need to stop taking some of your current medications. Please consult with the study team for specific guidance on your medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ifinatamab deruxtecan (I-DXd) is generally safe for individuals who have undergone multiple treatments. Most patients tolerate the drug well, and side effects are usually manageable. Although some unwanted effects have been reported, they are generally not severe.

In another study, I-DXd demonstrated promising results in patients with small cell lung cancer, suggesting potential safety for other cancer types as well, though further research is necessary. This trial marks the first time I-DXd is being tested in humans, with the primary goal of understanding its safety and patient tolerance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Ifinatamab deruxtecan (I-DXd) because it offers a novel approach to treating advanced solid tumors. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, I-DXd is an antibody-drug conjugate that specifically targets cancer cells, delivering a potent chemotherapy agent directly to them. This targeted delivery method has the potential to enhance treatment effectiveness while reducing damage to healthy cells, which could lead to fewer side effects. By focusing on these advanced mechanisms, I-DXd represents a promising step forward in cancer treatment.

What evidence suggests that I-DXd might be an effective treatment for advanced cancer?

Research has shown that ifinatamab deruxtecan (I-DXd) may help treat advanced solid tumors. One study demonstrated that the drug significantly shrank tumors in nearly half of the patients with advanced small cell lung cancer. The FDA has recognized the drug's potential by granting it Breakthrough Therapy Designation. Participants in this trial will receive I-DXd as monotherapy, either during the dose escalation phase or the dose expansion phase. Although I-DXd remains in the early stages of human testing, these initial results suggest it could be a valuable option for those who haven't had success with other treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that haven't responded to other treatments. Participants must be relatively active (ECOG score of 0 or 1), have at least one measurable tumor, and proper organ function. Specific cancers like head and neck, lung, bladder, sarcoma, endometrial cancer are included if standard treatments failed or aren't available.

Inclusion Criteria

Has an adequate treatment washout period prior to start of study treatment

Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

My prostate cancer is resistant to hormone therapy and has spread to bones only.

Exclusion Criteria

I have been treated with a specific type of cancer drug related to trastuzumab deruxtecan.

I have severe lung problems or need extra oxygen.

I am currently fighting an infection that needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluate the safety and tolerability and determine the maximum tolerated dose and the recommended dose for expansion of ifinatamab deruxtecan (I-DXd)

Variable

IV administration every 3 weeks

Dose Expansion

Investigate the safety, tolerability, and antitumor activity of I-DXd when administered as a single agent

Variable

IV administration every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ifinatamab deruxtecan (I-DXd)

Trial Overview The study tests a new drug called Ifinatamab deruxtecan (I-DXd) in two parts: first to find the safest high dose (Dose Escalation) and then to see how well it works at that dose (Dose Expansion). There's no set number of treatment cycles; patients benefitting may continue unless side effects become too severe.

How Is the Trial Designed?

Group I: Dose expansion Experimental Treatment 1 Intervention

Currently enrolling participants with advanced solid tumors who will receive I-DXd IV Q3W monotherapy at the recommended dose for expansion.

Group II: Dose escalation Experimental Treatment 1 Intervention

Participants with advanced solid tumors who received I-DXd IV Q3W monotherapy during dose escalation phase. Enrollment to this phase is currently closed.

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

Daiichi Sankyo Co., Ltd.

Lead Sponsor

Trials

116

Recruited

49,200+

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

The phase III DESTINY-Breast04 trial demonstrated that trastuzumab deruxtecan (T-DXd) is effective for patients with inoperable or metastatic HER2-low breast cancer, providing a new treatment option for this group.

Given the limited treatment options available for patients with HER2-low breast cancer, T-DXd is recommended as a new standard of care, highlighting its significance in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd: New Standard for HER2-Low Breast Cancer. [2022]

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 a phase II study involving 152 patients with HER2-mutant metastatic non-small-cell lung cancer, trastuzumab deruxtecan (T-DXd) showed a confirmed objective response rate of 49% at 5.4 mg/kg and 56% at 6.4 mg/kg, indicating robust antitumor activity.

The safety profile of T-DXd was generally manageable, with fewer severe adverse events reported in the 5.4 mg/kg group compared to the 6.4 mg/kg group, suggesting that the lower dose may be preferable for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial. Goto, K., Goto, Y., Kubo, T., et al.[2023]

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]

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) is an antibody-drug conjugate that combines an anti-HER2 antibody with a topoisomerase I inhibitor, showing a stable drug-to-antibody ratio in vivo compared to other similar drugs.

In a study involving monkeys, the concentrations of the drug and antibody decreased over time after administration, with the drug-to-antibody ratio dropping to about 2.5 over 21 days, indicating a gradual release of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transition of average drug-to-antibody ratio of trastuzumab deruxtecan in systemic circulation in monkeys using a hybrid affinity capture liquid chromatography-tandem mass spectrometry. Habara, H., Okamoto, H., Nagai, Y., et al.[2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02713-8/fulltext

690P Ifinatamab deruxtecan (I-DXd; DS-7300) in patients ... Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04145622

Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in ... This is a single group study of participants with advanced solid tumors who have not been cured by other treatments. It is the first time the drug will be ...

3. merck.com merck.com/news/ifinatamab-deruxtecan-granted-breakthrough-therapy-designation-by-u-s-fda-for-patients-with-pretreated-extensive-stage-small-cell-lung-cancer/

Ifinatamab Deruxtecan Granted Breakthrough Therapy ... Ifinatamab Deruxtecan Granted Breakthrough Therapy Designation by U.S. FDA for Patients with Pretreated Extensive-Stage Small Cell Lung Cancer.

4. daiichisankyo.us daiichisankyo.us/press-releases/-/article/ifinatamab-deruxtecan-demonstrated-clinically-meaningful-response-rates-in-patients-with-extensive-stage-small-cell-lung-cancer-in-ideate-lung01-phase-2-trial

Ifinatamab Deruxtecan Demonstrated Clinically Meaningful ... Download the PDF version of Article. September 07, 2025. An objective response rate of 48.2% was observed with ifinatamab deruxtecan in ...

5. 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.

6. daiichisankyo.us daiichisankyo.us/press-releases/-/article/ifinatamab-deruxtecan-granted-breakthrough-therapy-designation-by-us-fda-for-patients-with-pretreated-extensive-stage-small-cell-lung-cancer

Ifinatamab Deruxtecan Granted Breakthrough Therapy ... Ifinatamab Deruxtecan Granted Breakthrough Therapy Designation by U.S. FDA for Patients with Pretreated Extensive-Stage Small Cell Lung Cancer.

7. merck.com merck.com/news/ifinatamab-deruxtecan-demonstrated-clinically-meaningful-response-rates-in-patients-with-extensive-stage-small-cell-lung-cancer-in-ideate-lung01-phase-2-trial/

Ifinatamab Deruxtecan Demonstrated Clinically Meaningful ... Ifinatamab Deruxtecan Demonstrated Clinically Meaningful Response Rates in Patients with Extensive-Stage Small Cell Lung Cancer in IDeate-Lung01 ...

8. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/20833/21637/ACCP_IDXd_Tran_P042_IDPT01_Poster_FINAL.pdf

Pharmacokinetics and exposure–safety analyses across ... Pharmacokinetics and exposure–safety analyses across tumor types for ifinatamab deruxtecan (I-DXd) in the first-in-human IDeate-PanTumor01 ...