Autogene Cevumeran + Atezolizumab for Cancer

Recruiting at 50 trial locations

Overseen By Reference Study ID Number: GO39733 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: MAOIs, Immunosuppressives

Disqualifiers: Liver disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

272 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a personalized cancer vaccine and an immune-boosting drug in cancer patients. The vaccine teaches the body to attack cancer, while the drug helps immune cells find and kill hidden cancer cells. This approach aims to induce strong anti-tumor responses by selecting suitable vaccines based on the patient's existing immune system.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have had any anti-cancer therapy within 3 weeks before starting the study, and you should not be on systemic immunosuppressive medications within 2 weeks prior to starting. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab in treating cancer?

Atezolizumab has been shown to improve survival in patients with advanced non-small cell lung cancer and urothelial carcinoma, especially in those with high PD-L1 expression, and is generally well-tolerated. ^{1 2 3 4 5}

Is the combination of Autogene Cevumeran and Atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been studied in various cancers and generally has an acceptable safety profile. Common side effects include tiredness, reduced appetite, and nausea, while more serious effects like lung inflammation and liver issues are less common. However, specific safety data for the combination with Autogene Cevumeran is not provided in the available research. ^{1 6 7 8 9}

What makes the drug combination of Autogene Cevumeran and Atezolizumab unique for cancer treatment?

This drug combination is unique because Atezolizumab is a monoclonal antibody that blocks PD-L1, enhancing the immune system's ability to fight cancer, while Autogene Cevumeran is a personalized cancer vaccine designed to stimulate a specific immune response against tumor cells, offering a novel approach compared to standard treatments. ^{1 2 4 5 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with certain advanced cancers (like melanoma, lung, bladder, colorectal) that have worsened after standard treatment or where such treatments aren't suitable. Participants should be relatively healthy otherwise (ECOG 0-1), have a life expectancy of at least 12 weeks, and not have had recent major surgeries or immune system issues.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My kidneys are functioning well, with a creatinine clearance rate of at least 50 mL/min.

I have advanced NSCLC and haven't been treated with specific immune therapies.

Exclusion Criteria

I have not received neoantigen-specific or whole-tumor cancer vaccines, except as allowed.

I do not have an active brain tumor or untreated brain metastases.

I have had my spleen removed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Participants receive autogene cevumeran at escalated dosages, with or without atezolizumab, to evaluate safety and pharmacokinetics

8-12 weeks

Dose Exploration and Expansion

Participants receive autogene cevumeran and atezolizumab at various dose levels to explore and expand treatment efficacy and safety

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• Autogene Cevumeran

Trial Overview The study is testing Autogene Cevumeran alone and combined with Atezolizumab in patients with various advanced cancers. It's an early-phase trial to check the safety and how well these treatments work together while monitoring the body's immune response.

Participant Groups

Group I: Phase Ib: Dose Exploration: Autogene Cevumeran + Atezolizumab Experimental Treatment 2 Interventions

Non-small cell lung cancer (NSCLC) or melanoma cancer immunotherapy (CIT)-treated participants will receive autogene cevumeran (at dosage lower than maximum tolerated dose \[MTD\] based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.

Group II: Phase 1b Flat Dose Escalation: Autogene Cevumeran + Atezolizumab Experimental Treatment 2 Interventions

Participants will receive autogene cevumeran at escalated dosages along with atezolizumab at a fixed dose of 1200 milligrams (mg)

Group III: Phase 1b Expansion: Autogene Cevumeran + Atezolizumab (Serial Biopsy) Experimental Treatment 2 Interventions

CIT-naive patients with selected tumor types who consent to optional serial biopsies will receive autogene cevumeran (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a dixed dose of 1200 mg.

Group IV: Phase 1b Expansion: Autogene Cevumeran + Atezolizumab Experimental Treatment 2 Interventions

Participants with different indications as per inclusion criteria will receive autogene cevumeran (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.

Group V: Phase 1a Flat Dose Escalation: Autogene Cevumeran Experimental Treatment 1 Intervention

Participants will receive autogene cevumeran at escalated dosages.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]

4. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

5. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]