Clinical Trial: NCT03456063 - My Cancer Genome

NCT03456063

Description:

This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.

Related Conditions:

Non-Squamous Non-Small Cell Lung Carcinoma
Squamous Cell Lung Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT03456063

Trial Eligibility

Document

Title

Brief Title: A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)
Official Title: A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Clinical Trial IDs

ORG STUDY ID: GO40241
NCT ID: NCT03456063

Conditions

Non-Small-Cell Lung

Interventions

Drug	Synonyms	Arms
Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody	Tecentriq	Arm A: Atezolizumab + platinum-based chemotherapy
Placebo Comparator		Arm B: Placebo + platinum-based chemotherapy
Nab-paclitaxel	Abraxane	Arm A: Atezolizumab + platinum-based chemotherapy
Pemetrexed	Alimta	Arm A: Atezolizumab + platinum-based chemotherapy
Carboplatin		Arm A: Atezolizumab + platinum-based chemotherapy
Cisplatin		Arm A: Atezolizumab + platinum-based chemotherapy
Gemcitabine	Gemzar	Arm A: Atezolizumab + platinum-based chemotherapy

Purpose

Trial Arms

Name	Type	Description	Interventions
Arm A: Atezolizumab + platinum-based chemotherapy	Experimental	Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: carboplatin + pemetrexed carboplatin + nab-paclitaxel cisplatin + pemetrexed cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab	Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Nab-paclitaxel Pemetrexed Carboplatin Cisplatin Gemcitabine
Arm B: Placebo + platinum-based chemotherapy	Placebo Comparator	Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: carboplatin + pemetrexed carboplatin + nab-paclitaxel cisplatin + pemetrexed cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery	Placebo Comparator Nab-paclitaxel Pemetrexed Carboplatin Cisplatin Gemcitabine

Eligibility Criteria

        Inclusion criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB
             (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on
             the 8th edition of the AJCC/UICC staging system

          -  Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection
             with curative intent

          -  Adequate pulmonary and cardiac function to undergo surgical resection

          -  Measurable disease as defined by RECIST v1.1

          -  Adequate hematologic and end organ function

          -  Negative HIV test at screening

          -  Negative for active HBV and HCV at screening

          -  Adequate tissue for PD-L1 IHC assessment

        Exclusion criteria:

          -  NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma

          -  Mixed NSCLC and small cell lung cancer histology

          -  Any prior therapy for lung cancer

          -  Malignancies other than NSCLC within 5 years prior to randomization, with the
             exception of those with a negligible risk of metastasis or death treated expected
             curative outcome

          -  Non-squamous NSCLC histology with activating ALK and EGFR mutation

          -  Pregnant or lactating women

          -  History of autoimmune disease

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, or evidence of active of active pneumonitis on screening chest Computed
             Tomography (CT) scan

          -  Prior treatment with cluster of differentiation 137 (CD137) agonist or immune
             checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1
             therapeutic antibody

          -  Severe infection within 4 weeks prior to randomization

          -  Significant history of cardiovascular disease

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first.

Secondary Outcome Measures

Measure:	Pathological Complete Response (pCR)
Time Frame:	At time of surgery
Safety Issue:
Description:	pCR is defined as the absence of any viable primary tumor cells at the time of surgical resection in the primary tumor as assessed by central and local pathology laboratory.

Measure:	Major Pathological Response (MPR)
Time Frame:	At time of surgery
Safety Issue:
Description:	MPR is defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor, as assessed by central and local pathology laboratory.

Measure:	Overall Survival (OS)
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	OS is defined as the time from randomization to death from any cause during the course of the study.

Measure:	Investigator-Assessed EFS
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, as assessed by the investigator; or death from any cause, whichever occurs first.

Measure:	Disease-Free Survival (DFS)
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	DFS is defined as the time from the first date of no disease to local or distant recurrence (including occurrence of new primary NSCLC) or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up

Measure:	Objective Response (OR)
Time Frame:	Prior to surgery, up to approximately 84 days
Safety Issue:
Description:	Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1

Measure:	2-Year and 3-Year OS
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	The 2-year and 3-year OS rate is defined as the probability that a participant will be alive 2 years and 3 years after randomization, respectively.

Measure:	2-Year and 3-Year Independent Review Facility-Assessed EFS
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Independent Review Facility.

Measure:	2-Year and 3-Year Investigator-Assessed EFS
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Investigator.

Measure:	Change from baseline in HRQoL scores
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:	Change from baseline in HRQoL scores as assessed through use of the two-item GHS/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow-up assessments

Measure:	Percentage of Participants With Adverse Events (AEs)
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:

Measure:	Number and Severity of Surgical Related Adverse Events
Time Frame:	Up to approximately 81 months
Safety Issue:
Description:

Measure:	Minimum Observed Serum Atezolizumab Concentration (Cmin)
Time Frame:	Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 81 months)
Safety Issue:
Description:	Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

Measure:	Maximum Observed Serum Atezolizumab Concentration (Cmax)
Time Frame:	Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 81 months)
Safety Issue:
Description:	Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

Measure:	Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
Time Frame:	Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 81 months)
Safety Issue:
Description:

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Hoffmann-La Roche

Last Updated

August 5, 2021

Clinical Trials /

A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)