I-DXd + Atezolizumab for Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+51 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Daiichi Sankyo
Must not be taking: B7-H3 agents, CD137 agonists
Disqualifiers: Brain metastases, Cardiovascular disease, Autoimmune disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
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.
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.
12345Is 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.
36789What 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.
1391011Eligibility 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.
+10 more
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.
+21 more
Trial 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
Participant Groups
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.
7Treatment groups
Experimental Treatment
Group I: Cohort 2, Part B: Induction + Maintenance (I-DXd 8 mg/kg)Experimental Treatment3 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 Treatment3 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 Treatment3 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 Treatment3 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 Treatment2 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 Treatment2 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 Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Columbia University Hervert Irving Comprehensive Cancer CenterNew York, NY
Medical College of WisconsinMilwaukee, WI
NYU Langone Hospital - Long IslandMineola, NY
Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityChicago, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Daiichi SankyoLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited.
Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer. [2022]Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.
A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. [2023]Transformed small-cell lung cancer (T-SCLC) has an extremely poor prognosis, and no remedies based on immunotherapy have been evaluated among T-SCLC patients. We retrospectively analysed the efficacy and safety of combining atezolizumab with chemotherapy for T-SCLC.
Study: Atezolizumab Improves Survival in SCLC. [2019]Combining the PD-L1 inhibitor atezolizumab with platinum-based chemotherapy improves overall survival among patients with extensive-stage small cell lung cancer relative to chemotherapy alone. These findings could lead to a new first-line treatment option for patients with the disease.
Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]Programmed death-ligand 1 (PD-L1) protein is expressed in various cancers, including small-cell lung cancer (SCLC). Atezolizumab inhibits PD-L1 signaling, thus restoring tumor-specific T-cell immunity. Here, we report results from the first-in-human phase 1 PCD4989g study (NCT01375842) of atezolizumab, in a cohort of patients with relapsed/refractory SCLC.
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]Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC.
Atezolizumab: First Global Approval. [2019]Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.
Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy. [2020]Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC. We performed a literature search of PubMed, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference on Lung Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in comparison with docetaxel for second-line treatment of advanced NSCLC. Potential predictive biomarkers also have to be assessed.
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. [2022]Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population.
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]BACKGROUND Atezolizumab is an immune checkpoint inhibitor used as first-line treatment with carboplatin and etoposide chemotherapy for advanced small cell lung cancer. Immunochemotherapy treatment decisions can be affected by patients' physical ability. Because of the exclusion of patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 from clinical trials, treatment outcome evidence in this group is limited. CASE REPORT We present the case of a 75-year-old woman with an ECOG PS of 2 admitted with respiratory symptoms and diagnosed with advanced small-cell lung cancer. After managing exacerbation of COPD and decompensated heart failure, atezolizumab with carboplatin and etoposide was administered. After 2 cycles of immunochemotherapy, deterioration of health was observed, including anemia and thrombocytopenia. Because of the good response in imaging tests and restored balance of the patient condition, immunochemotherapy was continued. After 4 cycles of combined treatment, complete regression was achieved. No another adverse effects were observed. The patient was qualified for maintenance therapy with atezolizumab. In follow-up CT scan after 2 cycles of atezolizumab, progression was observed and patient was qualified for second-line treatment. CONCLUSIONS This report presents the case of an older patient with advanced small cell lung cancer and an ECOG status of 2 who responded to combined immunochemotherapy with atezolizumab, etoposide, and carboplatin. Adverse effects observed during immunotherapy were not a reason for discontinuation of the therapy. The assessment of the effectiveness of immunotherapy in patients with ECOG PS ³2 is difficult owing to the insufficient representation of this group in clinical trials.
Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). [2022]Atezolizumab is effective and well-tolerated in patients with extensive-stage small-cell lung cancer (ES-SCLC), but differences in response to systemic therapy exist between Asian and Caucasian patients. Here, we assess the efficacy and tolerability of atezolizumab in Japanese patients from the IMpower133 trial (NCT02763579).