I-DXd + Atezolizumab for Small Cell Lung Cancer

Recruiting at 54 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Daiichi Sankyo

Must not be taking: B7-H3 agents, CD137 agonists

Disqualifiers: Brain metastases, Cardiovascular disease, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 7

123 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol 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 specific medications with the trial team.

What data supports the effectiveness of the drug combination I-DXd and Atezolizumab for treating small cell lung cancer?

Research shows that adding atezolizumab to platinum-based chemotherapy improves overall survival for patients with extensive-stage small cell lung cancer compared to chemotherapy alone, suggesting it could be a promising first-line treatment option. ^{1 2 3 4 5}

Is the combination of atezolizumab and chemotherapy safe for treating small cell lung cancer?

Atezolizumab, when combined with chemotherapy, has been shown to be effective and safe in treating extensive-stage small cell lung cancer, according to real-life data and clinical trials. ^{3 6 7 8 9}

What makes the drug I-DXd + Atezolizumab unique for treating small cell lung cancer?

The combination of I-DXd (ifinatamab deruxtecan) and atezolizumab is unique because it combines a targeted therapy with an immune checkpoint inhibitor, potentially enhancing the immune system's ability to fight cancer cells in small cell lung cancer, a condition with limited treatment options. ^{1 3 9 10 11}

What is the purpose of this trial?

This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

Adults diagnosed with extensive stage-small cell lung cancer (ES-SCLC) needing first-line therapy can join. They must have good physical function and adequate organ function, agree to contraception use, and provide consent for biopsies if required. Women must test negative for pregnancy.

Inclusion Criteria

I am at least 18 years old or the legal adult age in my country.

I agree to provide biopsy samples before and during treatment.

My small cell lung cancer diagnosis is confirmed and I need first-line therapy.

Exclusion Criteria

I have severe lung problems due to other lung diseases.

I have been treated with drugs targeting B7-H3, like orlotamab or enoblituzumab.

I am on a daily steroid treatment of 10 mg or more, not counting inhalers, skin creams, or joint injections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive 4 cycles of 1L I-DXd induction therapy in combination with atezolizumab and carboplatin

12 weeks

4 visits (in-person, every 3 weeks)

Maintenance

Participants receive maintenance therapy with I-DXd and atezolizumab

Ongoing, up to 37 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Ifinatamab deruxtecan

Trial Overview The trial is testing the combination of I-DXd with atezolizumab, plus or minus carboplatin, in new ES-SCLC patients. It aims to assess safety and effectiveness as both initial treatment and ongoing maintenance therapy.

Participant Groups

Group I: Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg) Experimental Treatment 3 Interventions

Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Group II: Cohort 2, Part B: Induction + Maintenance (I-DXd 12 mg/kg) Experimental Treatment 3 Interventions

Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×minIV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Group III: Cohort 2, Part A: Induction + Maintenance (I-DXd 8 mg/kg) Experimental Treatment 3 Interventions

Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of 1L I-DXd induction therapy (8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 8 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Group IV: Cohort 2, Part A: Induction + Maintenance (I-DXd 12 mg/kg) Experimental Treatment 3 Interventions

Part A (Safety Run-in): Participants who are treatment-naive, newly diagnosed with ES-SCLC will receive 4 cycles of IL I-DXd induction therapy (12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W) + carboplatin (AUC 5 mg/ml×min IV Q3W) followed by maintenance therapy (I-DXd 12 mg/kg IV Q3W) + atezolizumab (1200 mg IV Q3W).

Group V: Cohort 1, Part B: Maintenance (I-DXd 8 mg/kg) Experimental Treatment 2 Interventions

Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 8 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W), starting at Cycle 1 Day 1.

Group VI: Cohort 1, Part B: Maintenance (I-DXd 12 mg/kg) Experimental Treatment 2 Interventions

Part B: Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W), starting at Cycle 1 Day 1.

Group VII: Cohort 1, Part A: Maintenance Only (I-DXd 12 mg/kg) Experimental Treatment 2 Interventions

Part A (Safety Run-in): Participants who must have received 4 cycles of 1L induction standard of care (SoC) therapy with best overall response of CR, PR, or SD will receive maintenance therapy only (I-DXd 12 mg/kg IV Q3W + atezolizumab 1200 mg IV Q3W). A 5-day surveillance period between each of the first 3 participants (up to a maximum of 9 participants) dosed is included as a safety measure.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Findings from Research

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

In a study of 349 patients diagnosed with extensive-stage small cell lung cancer (SCLC) in British Columbia, only 36% of those receiving platinum-doublet chemotherapy were eligible for first-line immune checkpoint inhibitors (ICI), highlighting a significant gap in treatment options for the majority of patients.

After one or two cycles of chemotherapy, an additional 11% of patients improved their performance status to become eligible for ICI, suggesting that treatment strategies may need to adapt to include patients with poorer initial health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer. Rittberg, R., Leung, B., Al-Hashami, Z., et al.[2022]

In a study of 47 patients with transformed small-cell lung cancer (T-SCLC), combining the PD-L1 inhibitor atezolizumab with chemotherapy resulted in a high objective response rate of 73% and significantly improved overall survival (20.2 months) compared to those who did not receive immunotherapy (7.9 months).

The combination therapy was well tolerated, showing a safety profile consistent with previous studies, suggesting it could be a promising treatment option for T-SCLC patients, particularly those with positive PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. Zhang, CY., Sun, H., Su, JW., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

In a retrospective study of 213 patients with extensive-stage small cell lung cancer (SCLC), atezolizumab combined with chemotherapy demonstrated a median progression-free survival (PFS) of 6.8 months and overall survival (OS) of 11.9 months, confirming its efficacy in a real-life setting.

The treatment was generally safe, with manageable hematological side effects, and factors like ECOG performance status and number of metastatic sites were found to influence both PFS and OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group. Gürbüz, M., Kutlu, Y., Akkuş, E., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, a PD-L1 inhibitor, has demonstrated good efficacy and safety as a second-line treatment for advanced non-small cell lung cancer (NSCLC) when compared to docetaxel, based on a comprehensive literature review.

The study highlights the need for further research into potential predictive biomarkers that could help identify which patients may benefit most from atezolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy. Jean, F., Tomasini, P., Barlesi, F.[2020]

In a phase 2 trial involving 287 patients with previously treated advanced non-small-cell lung cancer (NSCLC), atezolizumab significantly improved overall survival (12.6 months) compared to docetaxel (9.7 months), with a hazard ratio of 0.73, indicating a 27% reduction in the risk of death.

The efficacy of atezolizumab was found to correlate with PD-L1 expression levels on tumor cells and immune cells, suggesting that higher PD-L1 expression may predict better outcomes with this treatment, while atezolizumab also demonstrated a better safety profile with fewer severe adverse events compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Fehrenbacher, L., Spira, A., Ballinger, M., et al.[2022]

Atezolizumab combined with carboplatin and etoposide was effective in treating a 75-year-old woman with advanced small cell lung cancer and an ECOG Performance Status of 2, leading to complete regression after 4 cycles of treatment.

Despite experiencing some adverse effects like anemia and thrombocytopenia, the patient's therapy was continued due to positive imaging results, highlighting the potential for immunochemotherapy in patients typically excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. Dębczyński, M., Mojsak, D., Kuklińska, B., et al.[2022]

In Japanese patients with extensive-stage small-cell lung cancer (ES-SCLC), the addition of atezolizumab to standard chemotherapy (carboplatin and etoposide) resulted in a median overall survival of 14.6 months, compared to 11.9 months for the placebo group, indicating a significant improvement in survival rates.

Atezolizumab was well-tolerated among patients, with no treatment-related deaths reported, suggesting it is a safe option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Nishio, M., Sugawara, S., Atagi, S., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. [2023]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group. [2022]

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

Atezolizumab: First Global Approval. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. [2022]

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

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. [2022]

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

Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). [2022]