A clinical trial to compare tiragolumab plus atezolizumab with placebo plus atezolizumab in people with untreated advanced non-small cell lung cancer

1. Why is this study needed?
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer that usually develops in the tissues lining the lungs. In advanced NSCLC, the cancer spreads from the lungs to other parts of the body. Sometimes, NSCLC is present at a stage where it cannot be removed surgically (unresectable). Cancer treatment often includes a combination of drugs. However, these may not work for all patients, or at all times. Therefore, there is always a need to find new combinations of treatments.

This study is testing a combination of tiragolumab and atezolizumab. This combination is being developed as a treatment for advanced NSCLC that cannot be removed surgically or has spread to other parts of the body. In this study, the combination of tiragolumab and atezolizumab is experimental. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved the combination of tiragolumab and atezolizumab as a treatment for advanced NSCLC.

This study aims to compare the effects of tiragolumab plus atezolizumab versus placebo plus atezolizumab in people with advanced NSCLC that cannot be removed by surgery or has spread to other parts of the body. Placebo is a medicine without any active ingredients but looks the same and is taken the same way as the study drug.

2. Who can take part in the study?
People who were at least 18 years old with advanced NSCLC that could not be surgically removed or had spread to other parts of the body, took part in this study. Only people who tested positive for a protein called PD-L1 could participate in this study. PD-L1 is found in some cells, including cancer cells, which stops the body’s natural defence (immune system) from attacking them.

People could not take part in this study if they had other types of lung cancer or had received any prior treatments for lung cancer. Women who were pregnant, or breastfeeding could not participate in the study.

3. How does this study work?
People were screened to check if they were able to participate in the study. The screening period took place for about 28 days before the start of treatment.

Everyone who joined this study were split into two groups (Groups A and B) randomly (like flipping a coin). Participants are receiving either atezolizumab plus tiragolumab (Group A) or atezolizumab plus placebo (Group B), as drip into the vein (infusion) every 3 weeks. Treatment will continue until participants are experiencing benefit from the treatment, their cancer worsens, or they experience any unacceptable unwanted effects.

This is a ‘placebo-controlled’ study. This means that participants are put in a group that will receive a medicine or a group that will receive ‘placebo’. Comparing results from the different groups helps researchers know if any changes seen result from the study medicine or occur by chance. 

This is a double-blinded study. This means that neither the participants in the study nor the team running it will know which treatment is being given until the study is over. This is done to make sure that the results of the treatment are not affected by what people expect from the received treatment. However, the study doctor can find out which group the participant is in, if the participant’s safety is at risk.

During this study, the study doctor is meeting the participants every 3 weeks to check how well the treatment is working and any unwanted effects participants may have. Participants will have follow-up visits every 3 months after completion of treatment, during which the study doctor will check on the participant’s well-being. Total time of participation in the study will be approximately 59 months, depending on how the cancer responds to treatment. Participants have the right to stop study treatment and leave the study at any time if they wish to do so.

4. What are the main results measured in this study?
The main results measured in the study are to find out the approximate time from the start of treatment until the first incidence of cancer worsening, or participants dying due to any cause. The number of participants with unwanted effects and participants with cytokine-release syndrome (CRS) will also be checked. CRS occurs when the immune system reacts in an unusual way to an infection or cancer therapy. During this reaction, proteins called cytokines are released into the blood, causing symptoms like inflammation, fever, headache and rash.

Other key results measured in this study include:

• Number of participants who are cancer free or had at least a 30% decrease in the tumour size
• Time taken for the cancer to come back in a participant who was previously cancer free after undergoing treatment
• Time taken for a participant to have a significant worsening in physical and mental functioning
• How well the body processes tiragolumab and atezolizumab
• Number of participants whose bodies produce proteins against tiragolumab and atezolizumab
• How the participant's health and functioning are impacted by the treatment

5. Are there any risks or benefits in taking part in this study?
Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future. It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part were informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study were described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study drugs
Participants may have unwanted effects of the drugs used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants are having regular check-ups to see if there are any unwanted effects.

Participants were told about the known unwanted effects of tiragolumab and atezolizumab, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines.

Tiragolumab
Known unwanted effects include inflammation of the liver (hepatitis) with symptoms of yellowing of skin, pain in the stomach area, nausea, vomiting, itching, feeling tired or weak (fatigue), bleeding or bruising under the skin, and dark urine.

Atezolizumab
Known unwanted effects include back pain, cough, decreased appetite, fever, headache, itching of the skin (pruritus), rash, joint pain (arthralgia), lack of energy (asthenia), and shortness of breath (dyspnea).

Tiragolumab and atezolizumab are given as a drip into a vein. Known unwanted effects with infusion include irritation where the injection is given, fever, chills, rash, redness, swelling, itching, or pain. The study medicines may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.

What happens if I am unable to take part in this clinical trial?
If this clinical trial is not suitable for you, you will not be able to take part. Your doctor will suggest other clinical trials that you may be able to take part in or other treatments that you can be given. You will not lose access to any of your regular care.

For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov 

Trial-identifier: NCT04294810