GO29431 Phase III Study of MPDL3280A in Stage IV Non-Squamous NSCLC
Research type
Research Study
Full title
A Phase III, Open-Label, Randomized Study Of Atezolizumab (Anti-Pd-L1 Antibody) Compared With A Platinum Agent (Cisplatin Or Carboplatin) In Combination With Either Pemetrexed Or Gemcitabine For Pd- L1−Selected, Chemotherapy-Naive Patients With Stage IV Non-Squamous Or Squamous Non−Small Cell Lung Cancer
IRAS ID
181754
Contact name
Yvonne Summers
Contact email
Sponsor organisation
F. Hoffmann-La Roche Ltd
Eudract number
2014-003083-21
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 7 months, 31 days
Research summary
Summary of Research
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer. Patients diagnosed with NSCLC have poor prognosis with overall 5-year survival rate for advanced disease is 2-4%. Platinum-based chemotherapy regimens remain the first-line treatment for most locally advanced and metastatic NSCLC without a genetic mutation despite their toxicities. Hence the need for novel therapies that deliver an improved therapeutic index.
Immunotherapeutic agents that modulate immune cell activity offer an alternative approach that could potentially improve the prognosis of patients. MPDL3280A is an antibody that affects the immune system by blocking the programmed death-ligand 1 (PD-L1) pathway. The PD-L1 pathway is involved in decreasing the body’s immune response to fight cancer. By blocking the PD-L1 pathway, MPDL3280A may help the immune system stop or reverse the growth of tumours. MPDL3280A is currently being tested in multiple clinical trials and has shown demonstrated activity and was well tolerated in patients with advanced malignancies who failed standard-of-care therapies in a Phase Ia study.
The study purpose is to test the safety and efficacy of MPDL3280A compared with platinum-based therapies in PD-L1 selected chemotherapy-naïve patients with stage IV non-squamous NSCLC. Patients will be randomly assigned to receive open-label MPDL3280A (1200mg) every 21 days until loss of clinical benefit, toxicity or death or Cisplatin or Carboplatin + Pemetrexed (per investigator choice) every 21 days for 4 or 6 cycles by IV infusion (as per local standard of care) until disease progression, unacceptable toxicity or death.
Study procedures include: vital signs, physical examination, ECG, urine/blood samples for laboratory tests, tumour biopsy (if no previous samples are available), patient questionnaires and radiographic assessments to monitor the disease.
This study is being sponsored by F. Hoffmann-La Roche. Approximately 400 participants will take part in the study, with approximately 22 to be randomised in the UK.
Summary of Results
At the CCOD of 4 February 2020, a statistically significant OS improvement was not observed in the atezolizumab arm compared to the chemotherapy arm in the TC2/3 or IC2/3-WT population. Thus, OS was not formally tested in the TC1/2/3 or IC1/2/3-WT population.
At the CCOD of 4 February 2020, the exploratory updated analysis showed continued OS improvement in the atezolizumab arm compared to the chemotherapy arm in the TC3 or IC3-WT population.
The overall safety experience with atezolizumab was consistent with its known safety profile. There were no new safety signals. Atezolizumab was generally tolerated as well as chemotherapy. Immune-related toxicities were generally of low grade.
The results of the final analysis do not change the conclusions drawn from the primary analysis and the benefit-risk assessment remains positive in the TC3 or IC3-WT population.REC name
South West - Central Bristol Research Ethics Committee
REC reference
15/SW/0196
Date of REC Opinion
14 Oct 2015
REC opinion
Further Information Favourable Opinion