Ifinatamab Deruxtecan for Small Cell Lung Cancer

(IDeate-Lung02 Trial)

Recruiting at 271 trial locations

Overseen By Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must not be taking: B7-H3 agents, Topoisomerase inhibitors

Disqualifiers: Cardiovascular disease, Corneal disease, ILD, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 21-day cycles, up to 5 years

540 Participants Needed

Trial Summary

What is the purpose of this trial?

This study was designed to compare the efficacy and safety of I-DXd with treatment of physician's choice in participants with relapsed small cell lung cancer (SCLC).

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, there is a mention of an inadequate washout period, which suggests that some medications might need to be paused before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Ifinatamab Deruxtecan (DS-7300, I-DXd) for treating small cell lung cancer?

Trastuzumab deruxtecan, a similar drug, has shown effectiveness in treating various cancers, including breast, gastric, and non-small cell lung cancer, by significantly extending survival and showing high response rates. This suggests that Ifinatamab Deruxtecan, which may have similar properties, could potentially be effective for small cell lung cancer. ^{1 2 3 4 5}

What makes the drug Ifinatamab Deruxtecan unique for treating small cell lung cancer?

Ifinatamab Deruxtecan is unique because it is an antibody-drug conjugate, which means it combines an antibody (a protein that targets cancer cells) with a chemotherapy drug, allowing for targeted delivery to cancer cells, potentially reducing side effects compared to traditional chemotherapy. ^{6 7 8 9 10}

Research Team

Global Clinical Director

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

This trial is for adults over 18 with relapsed Small Cell Lung Cancer who've had at least one platinum-based treatment. They must have a good performance status, measurable cancer growth after recent therapy, and can have treated brain metastases if they're symptom-free.

Inclusion Criteria

I can provide a sample of my tumor that is large and high-quality enough for testing.

Participants must have at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator

Participants must sign and date the informed consent form prior to the start of any study-specific qualification procedures

Exclusion Criteria

I have a serious eye condition affecting my cornea.

I have not been treated with orlotamab, enoblituzumab, or similar drugs targeting B7-H3.

Participants who have inadequate washout period before randomization as specified in the protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Ifinatamab Deruxtecan (I-DXd) or Treatment of Physician's Choice (TPC) until a treatment discontinuation criterion is met

21-day cycles, up to 5 years

Day 1 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Treatment Details

Interventions

• Ifinatamab Deruxtecan

Trial Overview The study compares Ifinatamab Deruxtecan (I-DXd), a new drug, against the physician's choice of Topotecan, Lurbinectedin or Amrubicin in patients with relapsed SCLC to see which is more effective and safer.

Participant Groups

Group I: Ifinatamab deruxtecan (I-DXd) Experimental Treatment 1 Intervention

Participants randomized to receive 12 mg/kg I-DXd monotherapy on Day 1 of each 21-day cycle until unacceptable toxicity, progressive disease (PD), or withdrawal of consent as specified in the protocol.

Group II: Treatment of Physician's Choice (TPC) Active Control 3 Interventions

Participants randomized to receive topotecan, lurbinectedin, or amrubicin, as per investigator's choice and per locally approved label (indicated dose and frequency), until a treatment discontinuation criterion is met as specified in the protocol.

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

Findings from Research

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 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]

Trastuzumab deruxtecan (T-DXd) is a promising new antibody-drug conjugate that has been approved for treating HER2-positive metastatic breast cancer and gastric cancer, showing potential for use in other solid tumors as well.

T-DXd is expected to become the standard second-line treatment for HER2-positive metastatic breast cancer and may also benefit patients with hormone receptor-positive and triple-negative breast cancer that express low levels of HER2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. Perez, J., Garrigós, L., Gion, M., et al.[2022]

Trastuzumab deruxtecan has shown significant effectiveness in treating HER2-positive gastric and gastroesophageal junction cancers, extending overall survival and progression-free survival compared to standard chemotherapy in a randomized phase II trial.

The drug also demonstrated high response rates in phase II trials for HER2-mutant non-small cell lung cancer and HER2-positive colorectal cancer, suggesting its potential efficacy across various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan DESTINY for Some Cancers. [2021]

Trastuzumab deruxtecan (ENHERTU®) is an innovative treatment that combines an antibody targeting HER2 with a DNA topoisomerase I inhibitor, specifically designed for HER2-expressing solid tumors, including various types of cancer.

It received accelerated approval in the USA based on the promising results from the phase 2 DESTINY-Breast01 trial, which focused on patients with advanced HER2-positive breast cancer who had already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. Keam, SJ.[2020]

In a study involving 471 patients with relapsed/refractory small cell lung cancer, the combination of dinutuximab and irinotecan did not improve overall survival compared to irinotecan or topotecan alone, with median survival times of 6.9, 7.0, and 7.4 months respectively.

The safety profile showed that dinutuximab/irinotecan was associated with significant adverse events like neutropenia and anemia, but overall, irinotecan alone was found to be comparably effective to topotecan, suggesting that the combination therapy may not offer additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Edelman, MJ., Dvorkin, M., Laktionov, K., et al.[2022]

The ECI regimen, which combines irinotecan, cisplatin, and etoposide over three days, demonstrated a high response rate of 77% in advanced-stage small-cell lung cancer patients, indicating its efficacy as a treatment option.

The maximum tolerated dose of irinotecan was established at 140 mg/m², with manageable side effects including febrile neutropenia and grade 3 diarrhea, suggesting that the regimen is well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer. Briasoulis, E., Samantas, E., Kalofonos, H., et al.[2018]

The combination of irinotecan and cisplatin in a 3-week schedule for treating extensive-stage small-cell lung cancer (ES-SCLC) resulted in a high objective response rate of 89.3% among 28 previously untreated patients, indicating strong efficacy.

The treatment was associated with manageable toxicity, with significant grade 3/4 hematological toxicity (neutropenia) occurring in 26.9% of cycles, while non-hematological toxicities were rare, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of a 3-week schedule of irinotecan combined with cisplatin in previously untreated extensive-stage small-cell lung cancer. Lee, JE., Park, HS., Jung, SS., et al.[2018]

In a study of 54 patients with recurrent small cell lung cancer, both irinotecan combined with nedaplatin and irinotecan combined with cisplatin showed similar efficacy, with median progression-free survival of 5.4 months and 4.9 months, respectively.

The treatment regimens were found to be effective and tolerable, with mild toxicities; however, the irinotecan and nedaplatin combination had higher hematologic toxicity, while the irinotecan and cisplatin combination resulted in more diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A retrospective study of the efficacy and toxicity of irinotecan in combination with nedaplatin versus irinotecan in combination with cisplatin as salvage treatment in refractory or relapsed small cell lung cancer]. Yu, S., Wang, Y., Hu, X., et al.[2021]

In a phase II trial involving 80 patients with small-cell lung cancer (SCLC), the combination of irinotecan and carboplatin showed a 65% response rate in patients with brain metastases after just 2 cycles of treatment, indicating its efficacy.

The median survival for patients with brain metastases treated with this chemotherapy regimen was 6 months, which is comparable to existing literature showing response rates and survival ranging from 22% to 85% and 3 to 9 months, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for brain metastases in small-cell lung cancer. Chen, G., Huynh, M., Chen, A., et al.[2018]

References

1. 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]

2. England 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. [2020]

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

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. [2022]

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

Trastuzumab Deruxtecan DESTINY for Some Cancers. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II study of a 3-week schedule of irinotecan combined with cisplatin in previously untreated extensive-stage small-cell lung cancer. [2018]

9. China pubmed.ncbi.nlm.nih.gov

[A retrospective study of the efficacy and toxicity of irinotecan in combination with nedaplatin versus irinotecan in combination with cisplatin as salvage treatment in refractory or relapsed small cell lung cancer]. [2021]

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

Chemotherapy for brain metastases in small-cell lung cancer. [2018]