What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, such as immune checkpoint inhibitors like Atezolizumab (a PD-L1 inhibitor), often lead to immune-related adverse events (irAEs). These can include skin toxicities like vitiligo-like lesions, mucous membrane pemphigoid, and lichenoid reactions. Other side effects may involve the gastrointestinal system (colitis), endocrine system (thyroid dysfunction), and general symptoms like fatigue. Treatments similar to Autogene Cevumeran, which modulate the immune response, may also cause similar irAEs due to their mechanism of enhancing immune activity against tumors.

What prior FDA approvals exist?

FDA-approved treatments for head and neck cancers that involve immune response modulation and PD-L1 inhibition include pembrolizumab and nivolumab. Pembrolizumab, an anti-PD-1 antibody, has been approved for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on the KEYNOTE trials, which demonstrated improved overall survival and progression-free survival. Nivolumab, another anti-PD-1 antibody, was approved following the CheckMate 141 trial, which showed a significant survival benefit in patients with recurrent or metastatic HNSCC. These treatments are similar to the investigational use of autogene cevumeran (immune response modulation) and atezolizumab (PD-L1 inhibition) in ongoing clinical trials.

What other types of research exist?

Promising alternatives include Pembrolizumab, which has shown efficacy in the KEYNOTE-048 study as a first-line treatment either alone or in combination with chemotherapy based on PD-L1 status. Nivolumab, another immune checkpoint inhibitor, has demonstrated benefits in recurrent/metastatic settings. Additionally, the combination of Cetuximab and Nivolumab has shown potential in improving survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

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PD-L1 Inhibitor

Autogene Cevumeran + Atezolizumab for Cancer

Phase 1

Waitlist Available

Research Sponsored by Genentech, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Measured or calculated creatinine clearance >=50 milliliters per minute (mL/min) on the basis of the Cockcroft-Gault glomerular filtration rate estimation

Must not have

Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)

Previous splenectomy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to the immune system like inflammation in different organs, infusion-related reactions which can occur during or after receiving a drug intravenously, fatigue, digestive problems, changes in blood counts leading to increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have had my spleen removed.

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All my side effects from previous immune therapy, except stable hormone issues or vitiligo, have gone away.

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My cancer has spread to the lining of my brain and spinal cord.

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I have pain from my cancer that isn't relieved by treatment.

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I have high calcium levels in my blood that aren't managed.

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I haven't taken MAOI drugs in the last 3 weeks.

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I have active hepatitis B or C.

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I have a known immune system deficiency.

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I had cytokine treatment, but it's been over 6 weeks or 5 half-lives since my last dose.

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I frequently need procedures to remove excess fluid from my chest or abdomen.

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I have an active or latent tuberculosis infection.

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I haven't had a severe infection in the last 2 weeks.

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I have had a condition where my lymphocytes grow abnormally.

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I have not had severe infections in the last 4 weeks.

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I have not received a live vaccine in the last 4 weeks and do not plan to during the study.

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I haven't had any cancer treatment, including chemo, hormone therapy, or radiation, in the last 3 weeks.

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I do not have significant liver disease or a history of heavy alcohol use.

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I haven't had major surgery in the last 28 days and don't expect to need one during the study.

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I haven't taken any immune-weakening medications in the last 2 weeks.

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I have a history of lung scarring or inflammation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2019 Phase 3 trial • 1225 Patients • NCT02008227

36%

Fatigue

35%

Alopecia

24%

Diarrhoea

23%

Nausea

23%

Decreased appetite

22%

Anaemia

20%

Asthenia

19%

Cough

19%

Dyspnoea

16%

Myalgia

15%

Neutropenia

14%

Constipation

14%

Oedema peripheral

12%

Pyrexia

11%

Stomatitis

11%

Vomiting

11%

Neuropathy peripheral

10%

Arthralgia

Neutrophil count decreased

Rash

Dysgeusia

Headache

Paraesthesia

Pain in extremity

Mucosal inflammation

Back pain

Peripheral sensory neuropathy

Insomnia

Febrile neutropenia

Pneumonia

Lacrimation increased

Abdominal pain

Dry skin

Dizziness

Malaise

Urinary tract infection

Weight decreased

Haemoptysis

Nail disorder

Chest pain

Nasopharyngitis

Musculoskeletal pain

Bronchitis

Productive cough

Upper respiratory tract infection

Pruritus

Influenza like illness

Alanine aminotransferase increased

Aspartate aminotransferase increased

Syncope

Dehydration

Atrial fibrillation

Lower respiratory tract infection

Lung infection

Respiratory tract infection

Acute kidney injury

Chronic obstructive pulmonary disease

Pleural effusion

Depression

Musculoskeletal chest pain

100%

80%

60%

40%

20%

Study treatment Arm

Docetaxel

Atezolizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Phase Ib: Dose Exploration: Autogene Cevumeran + AtezolizumabExperimental Treatment2 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 + AtezolizumabExperimental Treatment2 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 Treatment2 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 + AtezolizumabExperimental Treatment2 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 CevumeranExperimental Treatment1 Intervention

Participants will receive autogene cevumeran at escalated dosages.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Head and Neck Cancers include immune response modulation and PD-L1 inhibition. Immune response modulation, such as with Autogene Cevumeran, involves enhancing the body's immune system to recognize and attack cancer cells more effectively. PD-L1 inhibitors like Atezolizumab work by blocking the PD-L1 protein on cancer cells, which normally helps them evade immune detection. By inhibiting this pathway, the immune system can better identify and destroy cancer cells. These mechanisms are crucial for patients with Head and Neck Cancers as they offer targeted approaches that can improve treatment efficacy and potentially reduce side effects compared to traditional therapies.

Immunotherapeutic Approaches to Head and Neck Cancer.The promise of immunotherapy in head and neck squamous cell carcinoma.