Extensive-stage Small Cell Lung Cancer
Conditions
Keywords
Chemotherapy, Aggressive malignancy, Programmed cell death ligand-1, Platinum-based chemotherapy
Brief summary
Study to determine the safety and tolerability profile of durvalumab with platinum (cisplatin or carboplatin) plus etoposide (EP) as first-line treatment in participants with extensive-stage small-cell lung cancer.
Detailed description
The study will be conducted in North America, Europe and Turkey. In this single arm study participants will be treated with with durvalumab alone and concurrently with platinum-based chemotherapy and etoposide during the study period until radiological disease progression, unless there is clinical progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met, as per investigator assessment.
Interventions
DRUGDurvalumab
Participants will receive durvalumab via IV infusion on Day 1 of each cycle.
DRUGCisplatin
Participants will receive cisplatin via IV administration on Day 1 of each cycle.
DRUGCarboplatin
Participants will receive carboplatin via IV administration Day 1 of each cycle.
DRUGEtoposide
Participants will receive etoposide via IV administration on days 1 to 3 of each cycle.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Histologically- or cytologically-documented ES-SCLC (stage IV \[T any, N any, M1 a/b\], or with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan (Brain metastases; must be asymptomatic or treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment) * Participants must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide * World Health Organization/ Eastern Cooperative Oncology Group performance status of 0 to 2 at enrollment Baseline computed tomography/ magnetic resonance imaging results of the brain, chest and abdomen (including liver and adrenal glands) within 28 days prior to the treatment initiation * No prior exposure to immune-mediated therapy including, but not limited to, other anti- CTLA-4, anti-Programmed cell death-1 (PD-1), anti- Programmed cell death ligand-1 (PD-L1), and anti-PD-L2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines * Adequate organ and marrow function * Body weight \> 30 kg * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants
Exclusion criteria
* History of allogeneic organ transplantation * Active or prior documented autoimmune or inflammatory disorders, systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent * History of another primary malignancy except for: * Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of Investigational medicinal product (IMP) and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease * History of leptomeningeal carcinomatosis and active primary immunodeficiency * Active infection including tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus * Any unresolved toxicity Common Terminology Criteria for Adverse Events Grade ≥ 2 from previous anticancer therapy * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients * Received prior systemic therapy for ES-SCLC * Medical contraindication to platinum (cisplatin or carboplatin)-etoposide-based chemotherapy * Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable * Planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care is allowed but must be completed before first dose of the study medication * Receipt of live attenuated vaccine within 30 days prior to the first dose of in IMP * Major surgical procedure within 28 days prior to the first dose of IMP * Participants who have received prior immunotherapy agents including anti-PD-1 or anti PD-L1 * Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab * Participation in another clinical study with an investigational product administered in the last 4 weeks * Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 180 days after the last dose of etoposide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs) | From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years. | Incidence of Grade 3 or higher adverse events to evaluate safety and tolerability profile of durvalumab + Platinum (cisplatin or carboplatin) plus etoposide (EP) treatment was assessed. |
| Number of Participants With Incidence of Immune Mediated Adverse Events (imAEs) | From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years. | Immune mediated adverse events (imAEs) were assessed to evaluate safety and tolerability profile of durvalumab + EP treatment. An imAE is defined as an AESI that is associated with drug exposure and is consistent with an immune-mediated mechanism of action (MOA) and where there is no clear alternate etiology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From screening until disease progression or the last evaluable assessment in the absence of progression, up to 2.5 years. | The efficacy of durvalumab + EP treatment by evaluating ORR according to RECIST 1.1 was assessed. The ORR will be assessed based on Investigator-assessed response to treatment of complete response (CR) and partial response (PR), per RECIST1.1. |
| Duration of Response (DoR) | From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years. | The efficacy of durvalumab + EP treatment by evaluating DoR according to RECIST 1.1 was assessed. The DoR is time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression. |
| Percentage of Participants Remaining in Response, 12 Months After First Documented Objective Response (DoR12) | From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years. | The efficacy of durvalumab + EP treatment by evaluating DoR12 according to RECIST 1.1 was assessed. |
| Progression-free Survival (PFS) | From first dose of study treatment until disease progression or death, up to 2.5 years. | Efficacy of durvalumab + EP treatment by evaluating PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was assessed. The PFS is the time from the first date of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from Investigational medicinal product (IMP) or received another anticancer therapy prior to progression. |
| Percentage of Participants Alive at 12 Months From First Date of Treatment (OS12) | From first dose of study treatment till 12 months. | The efficacy of durvalumab + EP treatment by evaluating OS12 was assessed. |
| Number of Participants With Adverse Events and Serious Adverse Events | From first dose of study treatment until 90 days after discontinuation, up to 2.5 years. | To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events and serious adverse events were assessed. |
| Number of Participants With Adverse Events of Special Interests | From first dose of study treatment until 90 days after discontinuation, up to 2.5 years. | To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP. AESIs for durvalumab include, but are not limited to, events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants, and/or hormone replacement therapy. This includes adverse events of special/ possible interest. |
| Overall Survival (OS) | From first dose of study treatment to death, up to 2.5 years. | Assessment of the efficacy of durvalumab + EP treatment by evaluating OS. The OS is the time from the first date of treatment until death due to any cause. |
| Percentage of Participants Alive and Progression-free at 12 Months From First Date of Treatment (PFS12) | From first date of study treatment until 12 months. | The efficacy of durvalumab + EP treatment by evaluating PFS12 according to RECIST 1.1 was assessed. |
Countries
Bulgaria, Canada, Czechia, Germany, Italy, Turkey (Türkiye)
Participant flow
Recruitment details
The study was conducted at 32 sites in 5 countries: Bulgaria, Czech Republic, Germany, Italy, Turkey. Study results are presented as of final data cut-off (DCO), 21Apr2024. After final DCO, no additional data was collected for the purpose of the analysis. Participants were allowed to continue the study drug until other drug supply options were available. The last subject's last visit was declared on 2Jan2025 once all participants were transferred to a rollover study or marketed product.
Pre-assignment details
Participants who met all the inclusion and none of the exclusion criteria were enrolled in this study. All study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab +EP Participants received durvalumab 1500 mg administered IV infusion concurrently with platinum-based chemotherapy and etoposide every 3 weeks (q3w) up to 6 cycles. Thereafter, durvalumab monotherapy was continued every 4 weeks post-chemotherapy unless specific treatment discontinuation criteria were met. | 152 |
| Total | 152 |
Baseline characteristics
| Characteristic | Durvalumab +EP |
|---|---|
| Age, Continuous | 64.0 Years |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 151 Participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 85 / 152 |
| other Total, other adverse events | 136 / 152 |
| serious Total, serious adverse events | 52 / 152 |
Outcome results
Primary
Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs)
Incidence of Grade 3 or higher adverse events to evaluate safety and tolerability profile of durvalumab + Platinum (cisplatin or carboplatin) plus etoposide (EP) treatment was assessed.
Time frame: From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab+EP | Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs) | 91 Participants |
Primary
Number of Participants With Incidence of Immune Mediated Adverse Events (imAEs)
Immune mediated adverse events (imAEs) were assessed to evaluate safety and tolerability profile of durvalumab + EP treatment. An imAE is defined as an AESI that is associated with drug exposure and is consistent with an immune-mediated mechanism of action (MOA) and where there is no clear alternate etiology.
Time frame: From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab+EP | Number of Participants With Incidence of Immune Mediated Adverse Events (imAEs) | 22 Participants |
Secondary
Duration of Response (DoR)
The efficacy of durvalumab + EP treatment by evaluating DoR according to RECIST 1.1 was assessed. The DoR is time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression.
Time frame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab+EP | Duration of Response (DoR) | 5.2 Months |
Secondary
Number of Participants With Adverse Events and Serious Adverse Events
To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events and serious adverse events were assessed.
Time frame: From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any Adverse event (AE) | 142 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE possibly related to any treatment | 109 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE of maximum CTCAE grade 3 or grade 4 | 85 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE of maximum CTCAE grade 3 or grade 4, possibly related to any treatment | 59 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE with outcome of death | 15 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE with outcome of death, possibly related to any treatment | 4 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE with outcome of death, possibly related to durvalumab | 0 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE with outcome of death, possibly related to EP | 4 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE leading to interruption or discontinuation of durvalumab | 40 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any AE leading to interruption or discontinuation of EP | 41 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome of death) | 52 Participants |
| Durvalumab+EP | Number of Participants With Adverse Events and Serious Adverse Events | Any SAE (including events with outcome of death), possibly related to any treatment | 16 Participants |
Secondary
Number of Participants With Adverse Events of Special Interests
To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP. AESIs for durvalumab include, but are not limited to, events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants, and/or hormone replacement therapy. This includes adverse events of special/ possible interest.
Time frame: From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab+EP | Number of Participants With Adverse Events of Special Interests | 82 Participants |
Secondary
Objective Response Rate (ORR)
The efficacy of durvalumab + EP treatment by evaluating ORR according to RECIST 1.1 was assessed. The ORR will be assessed based on Investigator-assessed response to treatment of complete response (CR) and partial response (PR), per RECIST1.1.
Time frame: From screening until disease progression or the last evaluable assessment in the absence of progression, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab+EP | Objective Response Rate (ORR) | 66.4 Percentage of participants |
Secondary
Overall Survival (OS)
Assessment of the efficacy of durvalumab + EP treatment by evaluating OS. The OS is the time from the first date of treatment until death due to any cause.
Time frame: From first dose of study treatment to death, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab+EP | Overall Survival (OS) | 16.4 Months |
Secondary
Percentage of Participants Alive and Progression-free at 12 Months From First Date of Treatment (PFS12)
The efficacy of durvalumab + EP treatment by evaluating PFS12 according to RECIST 1.1 was assessed.
Time frame: From first date of study treatment until 12 months.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab+EP | Percentage of Participants Alive and Progression-free at 12 Months From First Date of Treatment (PFS12) | 15.0 Percentage of participants |
Secondary
Percentage of Participants Alive at 12 Months From First Date of Treatment (OS12)
The efficacy of durvalumab + EP treatment by evaluating OS12 was assessed.
Time frame: From first dose of study treatment till 12 months.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab+EP | Percentage of Participants Alive at 12 Months From First Date of Treatment (OS12) | 59.8 Percentage of participants |
Secondary
Percentage of Participants Remaining in Response, 12 Months After First Documented Objective Response (DoR12)
The efficacy of durvalumab + EP treatment by evaluating DoR12 according to RECIST 1.1 was assessed.
Time frame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab+EP | Percentage of Participants Remaining in Response, 12 Months After First Documented Objective Response (DoR12) | 19.8 Percentage of participants |
Secondary
Progression-free Survival (PFS)
Efficacy of durvalumab + EP treatment by evaluating PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was assessed. The PFS is the time from the first date of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from Investigational medicinal product (IMP) or received another anticancer therapy prior to progression.
Time frame: From first dose of study treatment until disease progression or death, up to 2.5 years.
Population: SAF which consisted of all enrolled patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab+EP | Progression-free Survival (PFS) | 6.3 Months |