A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

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• Small Cell Lung Carcinoma 1,203

Small Cell Lung Carcinoma

1,203 studies on the registry are indexed under Small Cell Lung Carcinoma; 340 are open to participants now.

This study's enrollment of 503 is above the median of 56 across 1,030 interventional studies indexed under Small Cell Lung Carcinoma.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Atezolizumab + Carboplatin + Etoposide

  Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m\^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

  Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody · Drug: Carboplatin · Drug: Etoposide

• Active comparator
  Placebo + Carboplatin + Etoposide

  Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m\^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m\^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

  Drug: Carboplatin · Drug: Etoposide · Drug: Placebo

Interventions

• DrugAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

  Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

  Also known as: MPDL3280A, RO5541267, Tecentriq

• DrugCarboplatin

  Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

• DrugEtoposide

  Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

• DrugPlacebo

  Placebo intravenous infusion was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Primary outcomes

1. Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).

   Time frame: Baseline until PD or death, whichever occurs first (up to approximately 23 months)

2. Duration of Overall Survival (OS) in the Global Population

   OS is defined as the time from randomization to death from any cause.

   Time frame: Baseline until death from any cause (up to approximately 23 months)

Secondary outcomes

1. Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

   Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.

   Time frame: Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

2. Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

   DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first.

   Time frame: First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)

3. PFS Rate at 6 Months and at 1 Year in Global Population

   PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively.

   Time frame: 6 months, 1 year

4. OS Rate at 1 Year and 2 Years in the Global Population

   OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively.

   Time frame: 1 year, 2 years

5. Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population

   TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant.

   Time frame: Baseline until deterioration per symptom subscale (up to approximately 23 months)

6. Percentage of Participants With at Least One Adverse Event in the Global Population

   The percentage of participants with at least one adverse event in the global population.

   Time frame: Baseline until up to 90 days after end of treatment (up to approximately 49 months)

7. Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population

   The baseline prevalence and post-baseline incidence of ADAs against atezolizumab.

   Time frame: Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall)

8. Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population

   Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day.

   Time frame: Post-dose Day 1 of Cycle 1 (cycle length = 21 days)

9. Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population

   Atezolizumab pre-dose plasma concentration (Cmin) for each respective day.

   Time frame: Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)

10. Plasma Concentration of Carboplatin in the Global Population

    Plasma concentration of carboplatin in the Global population.

    Time frame: Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

11. Plasma Concentration of Etoposide in the Global Population

    Plasma concentration of etoposide in the Global Population.

    Time frame: Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

Baseline characteristics

Publications

• Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13. PubMed 33439693 ↗
• Mansfield AS, Kazarnowicz A, Karaseva N, Sanchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. doi: 10.1016/j.annonc.2019.10.021. Epub 2019 Dec 9. PubMed 31959349 ↗
• Nishio M, Sugawara S, Atagi S, Akamatsu H, Sakai H, Okamoto I, Takayama K, Hayashi H, Nakagawa Y, Kawakami T. Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Clin Lung Cancer. 2019 Nov;20(6):469-476.e1. doi: 10.1016/j.cllc.2019.07.005. Epub 2019 Jul 31. PubMed 31466854 ↗
• Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25. PubMed 30280641 ↗

Study documents

• Protocol and statistical analysis plan · Mar 6, 2019

Documents are hosted by the registry — open the source record to download them.