The efficacy of programmed cell death protein 1 (PD-1)programmed death-ligand 1 (PD-L1) inhibitors in solid tumor patients with different clinicopathological characteristics a meta-analysis

Lead Investigator: Hongliang Liu, Duke University
Title of Proposal Research: The efficacy of programmed cell death protein 1 (PD-1)programmed death-ligand 1 (PD-L1) inhibitors in solid tumor patients with different clinicopathological characteristics a meta-analysis
Vivli Data Request: 8921
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Cancer is the leading cause of death and a significant barrier to increasing life expectancy in many countries around the world. Immunotherapy is a type of cancer treatment that helps the immune system fight cancer. Immune checkpoints can dampen the immune response of some immune system cells in the blood, such as T cells, and prevent them from killing cancer tumor cells. Programmed cell death 1 (PD1) and programmed death ligand 1 (PD-L1) are both checkpoint proteins. PD-1 is a protein found on the surface of T cells in the immune system. When PD-1 binds to PD-L1 on the surface of the cancer cell, it basically tells the T cell to leave the cancer cell alone and enables it to “hide” from an immune attack and not be killed by the T cell. Checkpoint inhibitors (ICs) are a type of immunotherapy. They block these proteins that stop the T cells from attacking the cancer cells. PD1 and PD-L1 inhibitors are most promising and have been applied to the treatment of several types of cancer. Nonetheless, a large proportion of patients do not derive benefit from this approach, so it is important to identify predictable biomarkers (molecules in body fluids or tissues that can be indicators of normal or abnormal processes or disease) to select patients with the greatest potential benefit from immunotherapy.

Some biomarkers, such as the presence of PD-L1, tumor mutational burden (TMB: the number of changes found in the genes of cancer cells), and deficient mismatch repair (dMMR: cells that have many gene mutations), have been used to screen potential beneficiaries of immunotherapy, but the results are far from satisfactory. Moreover, it has been demonstrated that gender, age, smoking status, and many other factors have an impact on the human immune system, and studies have shown that these factors might affect the efficacy of PD-1/PD-L1 inhibitors. Nonetheless, it remains unclear how these factors affect the efficacy of immunotherapy.

This study will test the associations between the outcomes of solid tumor patients treated with PD1/PD-L1 inhibitors and clinicopathological characteristics (such as age, gender, ethnicity, or the presence of biomarkers mentioned above) and identify patients’ characteristics that can be used for the selection of patients with the greatest potential benefit from immunotherapy.

Requested Studies:

Phase 1/2a Study of Double-Immune Suppression Blockade By Combining a CSF1R Inhibitor (PLX3397) With An Anti-PD-1 Antibody (Pembrolizumab) To Treat Advanced Melanoma And Other Solid Tumors
Data Contributor: Daiichi Sankyo, Inc.
Study ID: NCT02452424
Sponsor ID: PLX108-14

A Phase II, Multicenter, Single-Arm Study OF Atezolizumab In Patients With PD-L1-Positive Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02031458
Sponsor ID: GO28754

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02108652
Sponsor ID: GO29293 (Cohort 2)

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02008227
Sponsor ID: GO28915

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02951767
Sponsor ID: GO29293 (Cohort 1)

A Multistage, Phase II Study Evaluating the Safety and Efficacy of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as First-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer
Data Contributor: Roche
Study ID: NCT02322814
Sponsor ID: WO29479

A Phase III, Double-Blinded, Randomized, Placebo-Controlled Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFV600 Mutation-Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Data Contributor: Roche
Study ID: NCT02908672
Sponsor ID: CO39262

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab and Taxane Based Therapy
Data Contributor: Roche
Study ID: NCT02924883
Sponsor ID: WO30085

A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367794
Sponsor ID: GO29437

A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367781
Sponsor ID: GO29537

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02302807
Sponsor ID: GO29294