A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (Morpheus Lung)

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung)

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC).

Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Atezolizumab; Drug: Cobimetinib; Drug: RO6958688; Drug: Tocilizumab; Drug: Docetaxel; Drug: CPI-444; Drug: Ipatasertib; Drug: Bevacizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Gemcitabine; Drug: Linagliptin; Drug: Sacituzumab Govitecan; Other: Radiation; Drug: Evolocumab; Drug: Tiragolumab; Drug: XL092; Drug: Camonsertib

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter Mac Callum Cancer Center
• France
  • Dijon, France, 21079
    • Centre Georges François Leclerc
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, France, 13005
    • Hôpital de la Timone
  • Montpellier, France, 34298
    • Institut Regional Du Cancer de Montpellier
  • Saint-Herblain, France, 44115
    • Institut de Cancerologie de L'Ouest
  • Toulouse, France, 31100
    • Institut Universitaire du cancer de Toulouse-Oncopole
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
  • Ramat Gan, Israel, 52620-00
    • Chaim Sheba Medical Center
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 08308
    • Korea University Guro Hospital
  • Songpa-gu, South Korea, 05505
    • University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 280146
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro-CIOCC
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario De Valencia
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• United Kingdom
  • London, United Kingdom, E1 2AT
    • Barts Cancer Institute
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

General Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1
• Life expectancy greater than or equal to 3 months
• Histologically or cytologically confirmed metastatic, non-squamous or squamous Non-Small Cell Lung Cancer (NSCLC)
• Measurable disease (at least one target lesion)
• Adequate hematologic and end-organ function
• Tumor accessible for biopsy
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Inclusion Criteria for Cohort 1

• No prior systemic therapy for metastatic NSCLC
• High tumor PD-L1 expression, defined as Tumor Proportion Score (TPS) or TCs >= 50% or TC3

Inclusion Criteria for Cohort 2

- Disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC

Exclusion Criteria

• Prior allogeneic stem cell or solid organ transplantation
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
• History of malignancy other than NSCLC within 2 years prior to screening
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

23

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stage 1: Cohort 1: Atezolizumab; Participants in the Atezolizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.
Experimental: Stage 1: Cohort 1: Atezolizumab + Cobimetinib; Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria. Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Cobimetinib; Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.
Experimental: Stage 1: Cohort 1: Atezolizumab + RO6958688; Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria. Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: RO6958688; Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle.; Drug: Tocilizumab; Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.
Active Comparator: Stage 1: Cohort 2: Docetaxel; Participants in the Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or disease progression. Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6958688 or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Docetaxel; Docetaxel is administered by IV on Day 1 of each 21 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Cobimetinib; Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Cobimetinib; Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + CPI-444; Participants in the Atezolizumab + CPI-444 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: CPI-444; CPI-444 is administered orally twice daily on Days 1- 21, of a 21 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + RO6958688; Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: RO6958688; Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle.; Drug: Tocilizumab; Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.
Experimental: Stage 1: Cohort 2: Atezolizumab + Ipatasertib; Participants in the Atezolizumab + Ipatasertib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Ipatasertib; Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Docetaxel; Participants in Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Docetaxel; Docetaxel is administered by IV on Day 1 of each 21 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Bevacizumab; Participants in Atezolizumab + Bevacizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Bevacizumab; Bevacizumab is administered by IV on Day 1 of each 21-day cycle.
Experimental: Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin; Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Pemetrexed; Pemetrexed is administered by IV on Day 1 of a 21 day cycle.; Drug: Carboplatin; Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle.
Experimental: Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin; Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Carboplatin; Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle.; Drug: Gemcitabine; Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21 day cycle.
Experimental: Stage 2: Cohort 2: Atezolizumab + RO6958688; Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: RO6958688; Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle.; Drug: Tocilizumab; Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.
Experimental: Stage 2: Cohort 2: Atezolizumab + Docetaxel; Participants in the Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who have received treatment with Atezolizumab + Docetaxel in Stage 1 will not receive this treatment in Stage 2.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Docetaxel; Docetaxel is administered by IV on Day 1 of each 21 day cycle.
Experimental: Stage 2: Cohort 2: Atezolizumab + Linagliptin; Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Linagliptin; Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan; Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Sacituzumab Govitecan; Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Evolocumab; Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Evolocumab; Evolocumab is administered subcutaneously at a dose of 140 mg on Days 1 and 15 of each 28-day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy; Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Bevacizumab; Bevacizumab is administered by IV on Day 1 of each 21-day cycle.; Other: Radiation; Radiotherapy up to 21 days
Active Comparator: Stage 1: Cohort 1: Atezolizumab + Tiragolumab; Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Tiragolumab; Tiragolumab is administered on Day 1 of each 21 day cycle.
Experimental: Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib); Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Tiragolumab; Tiragolumab is administered on Day 1 of each 21 day cycle.; Drug: XL092; XL092 is administered orally once a day on Day 1 to Day 21 of a 21 day cycle.; Other Names: Zanzalintinib
Experimental: Stage 1: Cohort 2: Atezolizumab + Camonsertib; Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Camonsertib; Camonsertib is administered orally on Days 1-3, Days 8-10 of a 21 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib; Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Bevacizumab; Bevacizumab is administered by IV on Day 1 of each 21-day cycle.; Drug: Camonsertib; Camonsertib is administered orally on Days 1-3, Days 8-10 of a 21 day cycle.
Experimental: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab; Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.	Drug: Atezolizumab; Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.; Drug: Bevacizumab; Bevacizumab is administered by IV on Day 1 of each 21-day cycle.; Drug: Tiragolumab; Tiragolumab is administered on Day 1 of each 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Percentage of Participants With Objective Response (OR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)	OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions, ≥4 weeks apart, during Stage 1 as determined by the investigator using RECIST v.1.1. Objective response rate (ORR) was defined as the percentage of participants with OR. CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off. The participant in the 'Stage 1 Cohort 2 (S1C2): Idasanutlin + Docetaxel' arm did not receive study treatment and was therefore excluded from the efficacy analyses.	Up to 50.4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Progression-free Survival (PFS) as Determined by Investigator According to RECIST V1.1	PFS was defined as the time from study treatment initiation to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. Kaplan-Meier (K-M) method was used to estimate PFS. The participant in the 'Stage 1 Cohort 2: Idasanutlin + Docetaxel' arm did not receive study treatment and was therefore excluded from the efficacy analyses.	From randomization to the first occurrence of PD or death (Up to 48.6 months)
Stage 1: PFS Rate at Month 6	PFS was defined as the time from study treatment initiation to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. The KM approach was used to estimate the percentage of participants who were event-free for PFS at Month 6. Percentages have been rounded off. The participant in the 'Stage 1 Cohort 2: Idasanutlin + Docetaxel' arm did not receive study treatment and was therefore excluded from the efficacy analyses.	At Month 6
Stage 1: Overall Survival (OS)	OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. K-M method was used to estimate OS. The participant in the 'Stage 1 Cohort 2: Idasanutlin + Docetaxel' arm did not receive study treatment and was therefore excluded from the efficacy analyses.	From randomization to death (Up to 67 months)
Stage 1: OS Rate at Month 6	OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at Month 6. Percentages have been rounded off. The participant in the 'Stage 1 Cohort 2: Idasanutlin + Docetaxel' arm did not receive study treatment and was therefore excluded from the efficacy analyses.	At Month 6
Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST V1.1	DOR was defined as the time from the first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurred first as per investigator assessment using RECIST v1.1. DOR was calculated for participants who had a best confirmed OR of CR/PR. CR and PR were defined as outlined in the description for ORR outcome measure. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, DOR was censored at the day of the last tumor assessment. K-M method was used to estimate DOR. The participant in the 'S1C2: Idasanutlin + Docetaxel' arm did not receive study treatment and was therefore excluded from the efficacy analyses.	From first occurrence of a documented OR until the time of documented PD or death (Up to 50.4 months)
Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST V1.1	DC was defined as stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1 Disease control rate (DCR) was defined as the percentage of participants with DC. CR was defined as the disappearance of all target & non-target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Percentages have been rounded off.	Up to 50.4 months
Stages 1 and 2: Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAEs = Serious AEs; AESIs = Adverse Events of Special Interest.	From baseline until 30 days (for AEs) or 135 days (for SAEs & AESIs) after the last dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurred first (Stage 1: up to 54.8 months; Stage 2: up to 43.1 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2017
• Primary Completion (Actual): October 14, 2025
• Study Completion (Actual): November 25, 2025

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Physical Phenomena; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Quinazolines; Docetaxel; Bevacizumab; Linagliptin; Pemetrexed; Gemcitabine; Carboplatin; Radiation; tocilizumab; ipatasertib; atezolizumab; Tiragolumab; cobimetinib; sacituzumab govitecan; evolocumab; ciforadenant
• Other Study ID Numbers: BO39610; 2017-001267-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No