I-DXd for Small Cell Lung Cancer

(IDeate-Lung01 Trial)

Not currently recruiting at 117 trial locations

Overseen By (US contact) 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, Cardiovascular disease, ILD, 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: 43

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ifinatamab deruxtecan (I-DXd) for individuals with Extensive-stage Small Cell Lung Cancer (ES-SCLC) who have already undergone platinum-based chemotherapy and up to three other treatments. The goal is to determine the optimal dose and evaluate its effectiveness against the cancer. Participants will receive the treatment at two different dose levels to identify which is most effective and safe. Those who have had at least two chemotherapy treatments for ES-SCLC and have experienced cancer progression might be suitable candidates. As a Phase 2 trial, the research focuses on assessing 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, if you are on chronic steroid treatment or have unresolved toxicities from previous cancer treatments, you may need to discuss this with the trial team.

Is there any evidence suggesting that ifinatamab deruxtecan (I-DXd) is likely to be safe for humans?

Research shows that ifinatamab deruxtecan (I-DXd) is generally safe for patients with advanced small cell lung cancer. In earlier studies, patients tolerated doses of 8 mg/kg and 12 mg/kg. The most common side effects included tiredness, nausea, and loss of appetite, typically mild to moderate.

One study found that the higher dose of 12 mg/kg caused expected side effects for this type of drug. While side effects can occur, they are not unexpected and can be managed during treatment.

Overall, evidence suggests that I-DXd is reasonably safe for individuals who have already tried other cancer treatments. ^{1 2 3 4 5}

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

Researchers are excited about Ifinatamab Deruxtecan (I-DXd) for small cell lung cancer because it offers a targeted approach that differs from the standard chemotherapy and immunotherapy options. I-DXd is an antibody-drug conjugate, meaning it combines an antibody that specifically targets cancer cells with a chemotherapy drug, delivering the treatment directly to the cancer while sparing more healthy cells. This targeted delivery could potentially improve effectiveness and reduce side effects compared to conventional treatments. Additionally, I-DXd is being tested in different dosages, which may optimize its efficacy and safety for patients.

What evidence suggests that ifinatamab deruxtecan (I-DXd) might be an effective treatment for small cell lung cancer?

Research has shown that ifinatamab deruxtecan (I-DXd) holds promise for treating extensive-stage small cell lung cancer (ES-SCLC). Studies have found that I-DXd works well in patients who have already tried other treatments. As an antibody-drug conjugate, it specifically targets cancer cells and delivers a drug to destroy them. In trials, patients with ES-SCLC, including those with cancer spread to the brain, responded well to the treatment. The FDA has granted this drug Breakthrough Therapy Designation, highlighting its potential effectiveness. Overall, early evidence supports I-DXd as a potentially effective option for those with previously treated ES-SCLC. Participants in this trial will receive I-DXd at either 8 mg/kg or 12 mg/kg to further evaluate its effectiveness. ^{1 2 3 6 7}

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 over 18 with ES-SCLC who've had at least one platinum-based treatment but no more than three prior therapies. They must have a measurable lesion not previously treated by radiation and show disease progression after the last therapy. Excluded are those with certain severe diseases, recent live vaccines, uncontrolled infections, or past hypersensitivity to similar drugs.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have received at least two cycles of platinum-based chemotherapy for extensive-stage disease.

My cancer has worsened after my last treatment.

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I have a serious eye condition affecting my cornea.

I haven't had a stroke, mini-stroke, or blood clot in the arteries in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Optimization (Part 1)

Participants are randomized to receive one of two dose levels of I-DXd (8 mg/kg or 12 mg/kg) to determine the recommended Phase 2 dose.

Up to 36 months

Every 21 days

Extension (Part 2)

All participants receive I-DXd at the selected dose of 12 mg/kg.

Up to 36 months

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ifinatamab Deruxtecan (I-DXd)

Trial Overview The study tests Ifinatamab Deruxtecan (I-DXd) in patients with ES-SCLC who've undergone previous chemotherapy. It aims to establish an effective dose based on safety and how the body processes the drug while assessing its ability to combat tumor growth.

How Is the Trial Designed?

Group I: Ifinatamab Deruxtecan (8 mg/kg) Experimental Treatment 1 Intervention

Participants will be randomized to receive I-DXd at 8 mg/kg.

Group II: Ifinatamab Deruxtecan (12 mg/kg) Experimental Treatment 1 Intervention

Participants will be randomized to receive I-DXd at 12 mg/kg. In Part 2, all participants will receive 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

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

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 a real-world study of 143 patients with HER2+ metastatic breast cancer, trastuzumab deruxtecan (T-DXd) demonstrated a high overall response rate of 68% and a median progression-free survival of 16 months, confirming its efficacy in routine clinical practice.

The safety profile of T-DXd was consistent with previous studies, with 59% of patients experiencing any-grade toxicity, primarily nausea and neutropenia, but no new safety concerns were identified, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. Botticelli, A., Caputo, R., Scagnoli, S., et al.[2023]

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]

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 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-02142

Ifinatamab Deruxtecan in Patients With Extensive-Stage ... This phase 2 trial evaluated the efficacy and safety of ifinatamab deruxtecan (I-DXd), a B7 homolog 3–directed antibody–drug conjugate, in ...

2. 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 Phase 2 ...

3. iaslc.org iaslc.org/iaslc-news/press-release/ifinatamab-deruxtecan-demonstrates-high-response-rate-previously-treated

Ifinatamab Deruxtecan Demonstrates High Response Rate ... Ifinatamab Deruxtecan Demonstrates High Response Rate in Previously Treated Extensive-Stage Small Cell Lung Cancer: Phase 2 IDeate-Lung01 Trial.

4. onclive.com onclive.com/view/infinatamab-deruxtecan-shows-encouraging-cns-activity-in-extensive-stage-small-cell-lung-cancer

Infinatamab Deruxtecan Shows Encouraging CNS Activity ... I-DXd showed intracranial efficacy and manageable safety in ES-SCLC with brain metastases, per data from the IDeate-Lung01 study.

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05280470

NCT05280470 | Ifinatamab Deruxtecan (I-DXd) in Subjects ... This 2-part study intends to define the recommended Phase 2 dose of ifinatamab deruxtecan (I-DXd) based on the efficacy, safety, and pharmacokinetics (PK) ...

7. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/d/datahub/wclc-2025_i-dxd_ahn_oral_final

Primary Analysis of the Phase 2 IDeate-Lung01 Study • The safety profile of I-DXd 12 mg/kg was manageable and consistent ... small cell lung cancer; LOT, line of therapy;. ORR, objective response rate ...