Atezolizumab Continuation for Cancer
(IMbrella B Trial)
Recruiting in Palo Alto (17 mi)
+89 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Hoffmann-La Roche
Must be taking: Atezolizumab
Must not be taking: Anti-cancer treatments
Disqualifiers: Pregnancy, Serious adverse events, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This is an open-label, multicenter, extension study. Patients who are receiving clinical benefit from atezolizumab monotherapy or atezolizumab in combination with other agent(s) or combination/comparator agent(s) during participation in a Genentech or Roche-sponsored study (the parent study), who are eligible to continue treatment and who do not have access to the study treatment locally, may continue to receive study treatment in this extension study following roll-over from the parent study.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.
What data supports the effectiveness of the drug Atezolizumab (Tecentriq) for cancer treatment?
Atezolizumab has shown effectiveness in treating advanced urothelial carcinoma and non-small cell lung cancer, with studies indicating it can prolong survival and has a manageable safety profile. In trials, it improved survival rates in patients with these cancers, even after other treatments had failed.12345
Is atezolizumab generally safe for humans?
Atezolizumab, also known as Tecentriq, has been evaluated in various clinical trials and is generally considered to have an acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious side effects can include pneumonia and liver inflammation. It has been approved for use in certain cancers, indicating that its benefits outweigh the risks for these conditions.16789
How does the drug atezolizumab differ from other treatments for cancer?
Atezolizumab is unique because it is a monoclonal antibody that targets PD-L1, a protein that helps cancer cells evade the immune system, thereby enhancing the body's immune response against tumors. It is used as a second-line therapy for certain cancers like urothelial carcinoma and non-small cell lung cancer, offering a novel approach compared to traditional chemotherapy.12349
Eligibility Criteria
This trial is for patients who were part of a previous Genentech/Roche study and benefited from Atezolizumab or other cancer treatments. They must not have access to these drugs locally, be able to continue treatment without health risks, and agree to contraception if applicable. Pregnant women or those with unresolved serious side effects are excluded.Inclusion Criteria
Time between the last dose of treatment received in parent study and first dose in extension study is no longer than the interruption period allowed in the parent study. First dose of study treatment in this extension study will be received within 7 days of the treatment interruption window allowed by the parent study
I am eligible to continue my current atezolizumab therapy or another study drug as per my initial study's protocol.
Negative serum pregnancy test within 7 days prior to start of study treatment in women of childbearing potential
See 3 more
Exclusion Criteria
Meet any of the study treatment discontinuation criteria specified in the parent study at the time of enrollment in this extension study
The treatment I am considering is available and approved for my condition in my country.
Any condition that, in the opinion of the investigator, would interfere with the interpretation of patient safety or place the patient at high risk for treatment-related complications
See 5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants continue to receive atezolizumab monotherapy or combination therapy as per the parent study protocol
21-day cycles
1 visit per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension
Participants may continue to receive study treatment in this extension study following roll-over from the parent study
Until unacceptable toxicity or loss of clinical benefit
Treatment Details
Interventions
- Atezolizumab (Checkpoint Inhibitor)
Trial OverviewThe extension study allows participants who saw benefits from Atezolizumab alone or in combination with other drugs in prior trials to continue receiving them. It's open-label and multicenter, meaning both the researchers and participants know what treatment is being given.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: Combined Agents with AtezolizumabExperimental Treatment14 Interventions
Participants will receive treatment of atezolizumab with combined agent(s) as directed per the parent study. Participants will receive agent(s) in combination with atezolizumab at the same dose and schedule, and with the same administration guidelines that were in effect at the time of participant discontinuation from the parent study.
Group II: Atezolizumab MonotherapyExperimental Treatment1 Intervention
Participants will receive atezolizumab by intravenous infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Group III: Comparator TreatmentActive Control9 Interventions
Participants will receive comparator treatment administration as directed per the parent study. Participants will receive comparator treatment at the same dose and schedule, and with the same administration guidelines that were in effect at the time of participant discontinuation from the parent study.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BC Cancer - VancouverVancouver, Canada
University of Colorado Cancer CenterAurora, CO
Yale University School Of MedicineTrumbull, CT
Advent Health OrlandoWinter Park, FL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Hoffmann-La RocheLead Sponsor
References
Atezolizumab: First Global Approval. [2019]Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.
[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq®) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.
Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials. In these studies, atezolizumab significantly prolonged overall survival (OS) relative to docetaxel, regardless of PD-L1 status. Increasing PD-L1 expression was associated with OS improvements. Atezolizumab also demonstrated efficacy in the phase II FIR and BIRCH trials, as assessed by objective response rates (ORRs) in patients with tumours expressing PD-L1. Higher ORRs were seen in patients with high PD-L1 expression. Atezolizumab had an acceptable, manageable tolerability profile, with a low incidence of immune-related adverse events. Therefore, atezolizumab is a valuable treatment option for patients with advanced NSCLC that has progressed during or after chemotherapy.
Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. [2020]Atezolizumab (Tecentriq®), a humanized, anti-programmed cell death ligand-1 (PD-L1) monoclonal antibody, in combination with bevacizumab, carboplatin and paclitaxel (ABCP) or with carboplatin and nab-paclitaxel (ACnP) has been approved as first-line treatment for metastatic nonsquamous NSCLC, based on results from the randomized IMpower150 and IMpower130 studies in chemotherapy-naïve patients with nonsquamous metastatic NSCLC. In IMpower150, ABCP prolonged progression-free survival (PFS) and overall survival (OS) relative to BCP, regardless of EGFR or ALK status, liver metastases at baseline or PD-L1 expression levels. In IMpower130, ACnP prolonged PFS and OS relative to CnP in patients without EGFR or ALK genetic aberrations. ABCP and ACnP had manageable tolerability profiles, which were consistent with the profile of the individual components of the regimen. Immune-related adverse events with ABCP and ACnP were largely mild or moderate in severity, and most were reversible with interruption of atezolizumab and initiation of appropriate treatment. Current evidence indicates that ABCP and ACnP are valuable emerging first-line treatment options for metastatic nonsquamous NSCLC.
Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. [2022]Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients.
Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. [2020]Atezolizumab is an inhibitor of PD-L1, which can lead to enhanced anticancer T-cell activity. We aimed to evaluate the safety, pharmacokinetics, and activity of atezolizumab in children and young adults with refractory or relapsed solid tumours, with known or expected PD-L1 expression.
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; P = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. Clin Cancer Res; 23(16); 4534-9. ©2017 AACR.
Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. [2020]Atezolizumab [anti-programmed death-ligand 1 (PD-L1)] selectively targets PD-L1 to block its interaction with receptors programmed death 1 and B7.1, thereby reinvigorating antitumor T-cell activity. We evaluated the long-term safety and activity of atezolizumab, along with biological correlates of clinical activity endpoints, in a cohort of patients with melanoma in an ongoing phase Ia study (NCT01375842).
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.