I-DXd for Advanced Cancer

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

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 used in humans, and will be in two parts. The primary purpose of the parts are: * Dose Escalation Part: To evaluate the safety and tolerability and to determine the maximum tolerated dose and the recommended dose for expansion of ifinatamab deruxtecan (I-DXd). * Dose Expansion Part: To investigate the safety, tolerability and antitumor activity of I-DXd when administered as a single agent. This study is expected to last approximately 5 years from the time the first participant is enrolled to the time the last participant is off the study. The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless: * they withdraw * their disease gets worse * they experience unacceptable side effects.

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.

What data supports the effectiveness of the drug Ifinatamab deruxtecan (I-DXd) for advanced cancer?

Trastuzumab deruxtecan, a similar antibody-drug conjugate, has shown effectiveness in treating various cancers, including HER2-low breast cancer and HER2-positive gastric cancer, by delivering a potent cancer-killing agent directly to cancer cells. This suggests that Ifinatamab deruxtecan, which is also an antibody-drug conjugate, may have potential effectiveness in treating advanced cancer. ^{1 2 3 4 5}

What makes the drug Ifinatamab deruxtecan (I-DXd) unique for treating advanced cancer?

Ifinatamab deruxtecan (I-DXd) is unique because it is an antibody-drug conjugate (ADC) that targets the B7-H3 protein, which is often found on cancer cells. This approach allows the drug to deliver a potent chemotherapy agent directly to the cancer cells, potentially reducing damage to healthy cells and improving treatment effectiveness. ^{1 2 3 4 6}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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) 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) 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]

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]

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) 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]

References

1. Japan 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. [2023]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2023]

6. England 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. [2023]