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A Study to Evaluate the Optimal Dose, Adverse Events and Change in Disease Activity of Intravenous ABBV-706 in Combination With Atezolizumab Versus Standard of Care as First-Line Treatment in Adult Participants With Previously Untreated Extensive Stage Small Cell Lung Cancer

Not Applicable
Not yet recruiting
Conditions
Small Cell Lung Cancer
Interventions
Registration Number
NCT07155174
Lead Sponsor
AbbVie
Brief Summary

Small cell lung cancer (SCLC) is characterized by aggressive and rapid growth and a tendency to develop early spread to distant sites including mediastinal lymph nodes, liver, bones, adrenal glands, and brain. The purpose of this study is to assess safety, dose, change in disease activity of ABBV-706 given with atezolizumab, compared to standard of care (SOC) treatment (etoposide, carboplatin, atezolizumab, and optional lurbinectedin).

ABBV-706 is an investigational drug being developed for the treatment of SCLC. There are multiple treatment arms in this study. Participants will either receive ABBV-706 given with atezolizumab, at 1 of 2 doses, or SOC. Approximately 730 adult participants will be enrolled in the study across sites worldwide.

In the phase 2 (safety lead-in) , participants with SCLC will receive intravenous (IV) ABBV-706 in 1 of 2 doses with IV atezolizumab, or IV SOC. In the phase 2 (expansion) portion of the study, participants with SCLC will receive IV ABBV-706 in 1 of 2 doses with atezolizumab, or IV SOC, until the optimal dose of ABBV-706 is determined. In the phase 3 (registrational) portion of the study, participants with SCLC will receive IV ABBV-706 in at the optimized dose with atezolizumab, or IV SOC. The estimated duration of the study is up to 69.5 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
730
Inclusion Criteria
  • Diagnosis of histologically or cytologically confirmed extensive stage small cell lung cancer (ES-SCLC) requiring treatment with first line therapy.
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 during the screening period prior to the first dose of study treatment.
  • Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
  • Suspected brain metastases at screening should have a computed tomography (CT)/ magnetic resonance imaging (MRI) of the brain prior to study entry.
Exclusion Criteria
  • Have received any kind of treatment for limited stage small cell lung cancer (LS-SCLC).
  • Known active/symptomatic central nervous system (CNS) metastases should be excluded.
  • History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest computed tomography (CT) scan should be excluded.
  • Have any clinically significant conditions that would adversely affect the participant's participation in the study, and the subject should have a life expectancy of at least 3 months.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Phase 2 (Safety Lead-In): ABBV-706 Dose AABBV-706Participants will receive ABBV-706 dose A in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): ABBV-706 Dose BAtezolizumabParticipants will receive ABBV-706 dose B in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): SOCEtoposideParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): SOCLurbinectedinParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 3 (Registrational): ABBV-706 Optimized DoseABBV-706Participants will receive ABBV-706 at the optimized dose in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 3 (Registrational): ABBV-706 Optimized DoseAtezolizumabParticipants will receive ABBV-706 at the optimized dose in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): ABBV-706 Dose AAtezolizumabParticipants will receive ABBV-706 dose A in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): ABBV-706 Dose BABBV-706Participants will receive ABBV-706 dose B in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): ABBV-706 Dose BAtezolizumabParticipants will receive ABBV-706 dose B in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): Stand of Care (SOC)AtezolizumabParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): Stand of Care (SOC)CarboplatinParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): ABBV-706 Dose AABBV-706Participants will receive ABBV-706 dose A in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): SOCCarboplatinParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): Stand of Care (SOC)EtoposideParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 2 (Safety Lead-In): Stand of Care (SOC)LurbinectedinParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): ABBV-706 Dose AAtezolizumabParticipants will receive ABBV-706 dose A in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): ABBV-706 Dose BABBV-706Participants will receive ABBV-706 dose B in combination with atezolizumab, as part of the approximately 69.5 month study duration.
Phase 2 (Expansion): SOCAtezolizumabParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin), as part of the approximately 69.5 month study duration.
Phase 3 (Registrational): SOCAtezolizumabParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin outside the United States of America), as part of the approximately 69.5 month study duration.
Phase 3 (Registrational): SOCLurbinectedinParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin outside the United States of America), as part of the approximately 69.5 month study duration.
Phase 3 (Registrational): SOCEtoposideParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin outside the United States of America), as part of the approximately 69.5 month study duration.
Phase 3 (Registrational): SOCCarboplatinParticipants will receive SOC (etoposide, carboplatin, atezolizumab, and optional lurbinectedin outside the United States of America), as part of the approximately 69.5 month study duration.
Primary Outcome Measures
NameTimeMethod
Number of Participants with Adverse Events (AE)sUp to 69.5 Months

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Phase 2: Progression-Free Survival (PFS) Based on Investigator AssessmentUp to Approximately 24 Months

PFS is defined as the time from randomization to the first documentation of radiological progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator or death from any cause, whichever occurs first.

Phase 3: Overall Survival (OS)Up to Approximately 28 Months

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

Secondary Outcome Measures
NameTimeMethod
Phase 2: Overall Response (OR) as Measured by Overall Response Rate (ORR) Based on Investigator AssessmentUp to Approximately 24 Months

OR is defined as participants achieving a best overall response (BOR) of confirmed complete response (CR)/partial response (PR) per RECIST v1.1 as determined by investigator prior to initiation of subsequent anti-cancer therapy. OR will be summarized by ORR, defined as the proportion of subjects achieving OR and will be summarized for each arm with its associated 95% confidence interval (CI).

Phase 2: Duration of Response (DoR) Based on Investigator AssessmentUp to Approximately 24 Months

DoR is defined as time from the initial response of CR/PR until the first documentation of radiographical PD according to RECIST v1.1 by investigator or death from any cause, whichever occurs first.

Phase 3: OR Based on Investigator AssessmentUp to Approximately 24 Months

OR is defined as participants achieving a BOR of confirmed CR/PR per RECIST v1.1 as determined by investigator prior to initiation of subsequent anti-cancer therapy. OR will be summarized by ORR, defined as the proportion of subjects achieving OR and will be summarized for each arm with its associated 95% CI.

Phase 2: Disease Control (DC) Based on Investigator AssessmentUp to Approximately 24 Months

DC is defined as achieving an OR or stable disease (SD) according to RECIST v1.1 by investigator at any time prior to subsequent anti-cancer therapy.

Phase 2: OSUp to Approximately 28 Months

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

Phase 3: PFS Based on Investigator AssessmentUp to Approximately 24 Months

PFS is defined as the time from randomization to the first documentation of radiological PD according to RECIST v1.1 per investigator or death from any cause, whichever occurs first.

Phase 3: Percentage of Participants with Change from Baseline in Key Lung Cancer Symptoms as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQLC13)Up to 12 Weeks

The EORTC QLQ-LC13 is a lung cancer specific module and consists of 13 questions assessing lung cancer-associated symptoms and treatment-related effects, including one multiple-item scale to assess dyspnea and a series of single items assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain, and pain medication. Each item is assessed on a Likert scale from 1 (not at all) to 4 (very much).

Phase 3: Percentage of Participants with Change from Baseline in Physical Functioning as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)Up to 12 Weeks

Health-related quality-of-life and symptoms will be assessed with the EORTC QLQ-C30, version 3.0. The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a (GHS/QoL) scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4 point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).

Phase 3: Percentage of Participants with Change from Baseline in GHS/QoL as measured by the EORTC QLQ-C30Up to 12 Weeks

Health-related quality-of-life and symptoms will be assessed with the EORTC QLQ-C30, version 3.0. The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a GHS/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4 point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).

Phase 3: DoR Based on Investigator AssessmentUp to Approximately 24 Months

DoR is defined as time from the initial response of CR/PR until the first documentation of radiographical PD according to RECIST v1.1 by investigator or death from any cause, whichever occurs first.

Phase 3: DC Based on Investigator AssessmentUp to Approximately 24 Months

DC is defined as achieving an OR or SD according to RECIST v1.1 by investigator at any time prior to subsequent anti-cancer therapy.

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