I-DXd + Atezolizumab for Small Cell Lung Cancer

Recruiting at 77 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a new combination of treatments for people with extensive-stage small cell lung cancer (ES-SCLC). It involves two main drugs: ifinatamab deruxtecan (I-DXd) and atezolizumab, an immune system booster, sometimes combined with carboplatin, a chemotherapy drug. The trial includes different parts, with some participants receiving only maintenance treatment and others receiving a combination of treatments. It is designed for individuals who have either just started treatment for ES-SCLC or have completed four cycles of standard first-line therapy and are doing well. Participants must have a confirmed diagnosis of ES-SCLC and require first-line therapy. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both ifinatamab deruxtecan (I-DXd) and atezolizumab are promising in terms of safety for treating extensive-stage small cell lung cancer (ES-SCLC). Previous studies on ifinatamab deruxtecan found it consistently safe, with side effects similar to those expected for this type of cancer drug.

Atezolizumab, when combined with chemotherapy, has also demonstrated an acceptable safety profile. Studies indicate that patients receiving atezolizumab with chemotherapy lived longer, and the treatment was generally well-tolerated.

Since this trial is in its early stages, the main goal is to assess the safety of combining these treatments. While specific side effects of this combination aren't detailed here, earlier studies have shown that both drugs are manageable on their own. Participants should be aware that, as with any trial, unknown risks could arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ifinatamab deruxtecan (I-DXd) and atezolizumab for treating small cell lung cancer (SCLC) because it introduces a novel approach to targeting cancer cells. Unlike standard chemotherapy, I-DXd is an antibody-drug conjugate, which means it specifically delivers cancer-killing agents directly to the cancer cells, minimizing damage to healthy cells. Additionally, atezolizumab is an immune checkpoint inhibitor, which helps activate the immune system to better fight cancer. Together, these treatments offer a dual approach by not only directly attacking the cancer cells but also enhancing the body's immune response, potentially leading to more effective and targeted treatment outcomes.

What evidence suggests that this trial's treatments could be effective 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). In earlier studies, I-DXd significantly shrank tumors in many patients who had already received treatment. In this trial, some participants will receive I-DXd combined with atezolizumab. Atezolizumab, when used with chemotherapy, has extended the lives of patients with ES-SCLC. These treatments work differently: I-DXd delivers a drug directly to the tumor to kill cancer cells, while atezolizumab boosts the immune system to fight the cancer. Early evidence suggests that combining these treatments could offer a powerful new option for people with this type of lung cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

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 agree to provide biopsy samples before and during treatment.

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

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

Exclusion Criteria

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

I have severe lung problems due to other lung diseases.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + 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. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + 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. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + 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 1L 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. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + 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 starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 8 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W

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 starting at Cycle 1 Day 1. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + atezolizumab 1200 mg IV Q3W.

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. Maintenance therapy consisting of I-DXd 12 mg/kg (or a lower dose based on data for I-DXd collected during the study) + 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

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12563583/

Effectiveness of Atezolizumab in Addition to Chemotherapy in ... Atezolizumab showed effectiveness and manageable safety consistent with clinical trials, supporting its use in routine ES-SCLC treatment.

2. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of extensive SCLC. IFCT-1905 CLINATEZO studied consecutive patients receiving ...

5. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life More patients lived longer with TECENTRIQ + chemotherapy ... Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11880126/

Efficacy and safety analysis of atezolizumab continuation ... The IMpower 133 trial demonstrated that combining atezolizumab with chemotherapy significantly enhanced survival, establishing chemo-immunotherapy as the ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.