AZ, Innate's checkpoint inhibitor monalizumab flunks phase 3 test

AstraZeneca has abandoned a phase 3 trial of its experimental immuno-oncology candidate monalizumab in head and neck cancer, after an interim analysis suggested it was unlikely to show a benefit.

The INTERLINK-1 trial was testing monalizumab – an NKG2A receptor inhibitor – in combination with EGFR-targeting antibody cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) previously treated with PD-1/PD-L1-targeted immunotherapies.

AZ licensed rights to monalizumab (formerly IPH2201) from France's Innate Pharma in 2018, after taking an option on the drug four years earlier in a deal that included an upfront payment of $250 million plus milestone payments, including $100 million due on the start of phase 3 testing.

Shares in Innate Pharma started to slide after this morning's announcement and were down almost 17% at the time of writing.

NKG2A is a checkpoint receptor thought to inhibit the anticancer activity of natural killer (NK) and cytotoxic CD8+ T-cells.

The results of INTERLINK-1 run counter to encouraging findings in a single-arm phase 1b/2 trial of monalizumab/cetuximab in SCHHN patients, which showed an overall response rate of 27.5% with the combination, as well as progression-free survival of five months and overall survival of more than ten months when after PD-1/PD-L1 therapy.

AZ is still testing the drug in the phase 3 PACIFIC-9 trial, looking at its PD-L1 checkpoint inhibitor Imfinzi (durvalumab) plus either monalizumab or anti-CD73 monoclonal antibody oleclumab in patients with non-small cell lung cancer (NSCLC) who have not progressed after first-line chemoradiotherapy.

It is also being tested alongside Imfinzi in phase 2 across multiple solid tumour types, including in the NeoCOAST-2 study as neoadjuvant (pre-surgery) treatment for early-stage lung cancer.

"While we are disappointed with the outcome of this study, the findings are certain to advance our understanding of the role of immunotherapy in this setting," said Mondher Mahjoubi, Innate Pharma's chief executive.

"We remain confident in the development program for monalizumab in lung cancer, where encouraging data has been previously reported from the randomized, Phase 2 COAST and Neo-COAST studies," he added.

How we test vacuums: Homes & Gardens' expert process

An example of how we test vacuums: a range of different tested vacuums all lined up in a row

The best vacuums transform a boring chore into effortless cleaning – as long as you pick the right one. Our team of experts have years of vacuum testing experience, so they are well-placed to offer trustworthy advice on the best vacuums.

We test every vacuum in our dedicated test center. Before testing, we thoroughly research the special features and claims of the vacuums. With these notes, we test the vacuums on a range of floor types and debris, so that we have reliable evidence of how each vacuum can cope with daily life. We scatter everything from hair to cereal on linoleum, carpet, and hardwood floors.

These tests are standardized, so we can compare every vacuum directly. Even our most budget model and our luxurious spend are put through the same process. As a result, we have hands-on experience and can be certain in our convictions of which vacuum is best suited to which house. We have an overview of the best vacuums on the market in our buying guides for cordless, pet hair, robot, and overall vacuums.

Shark Stratos review

With years of vacuuming experience and expertise, our testers have their fingers on the pulse. We keep an eye on updates to household names, but are always speaking to experts and listening to the market. If there is a new vacuum from a small brand that is performing well, we make sure to give them a fair test.

We know that different homes require different appliances, so ensure that we are testing a range of price points and features. We test upright, cordless, robot, smart, compact, and specialized pet hair vacuums. This means that we know the strengths and weaknesses of a range of vacuums. We also have some of the vacuums tested in homes, to see how well they perform outside of ideal conditions in our test center. This is especially important in our tests of the best vacuums for pet hair, which need testing on real dog and cat fur.

We make a point of being editorially independent. If a vacuum doesn’t perform, no money or gifts from public relations teams will convince us that it’s good. We only tell the truth and will let you know which vacuums are genuinely good.

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Hoover Blade+ vacuuming cereals off linoleum floor

We test on the three most common types of flooring, so we know how every vacuum performs in every home. Each test is repeated across linoleum, carpet, and wood flooring. Linoleum is easy to clean but shows dirt quickly, so it’s an unforgiving surface when testing vacuums. Carpet is much trickier to clean, as the fibers wrap around dirt and make it hard to vacuum away. It also shows us how a vacuum might perform on an area rug or a car footwell. Wood floors are similar to linoleum, but are much trickier to clean thanks to gaps between the floorboards that can easily trap dust and hair. Wood also reveals if the wheels on a vacuum scratch your flooring.

These tests let us see which vacuums are suited to which households. It might be the case - as in our review of the Dyson Ball Animal 3 - that a vacuum that excels on carpet is poor on linoleum. It can show us that a vacuum like Bissell ICONPet will have a small apartment with laminate floors spotless in minutes, but struggle to clean a big, carpeted home.

The SEBO upright vacuum collecting flour and sugar from wooden floors

We scatter flour and sugar across linoleum, hardwood, and carpet floors. Not only are these common messes on the kitchen floor, they’re also a good proxy for dust and dead skin. If a vacuum can handle this, it’ll be good for light use. Flour is a good visual test for every vacuum, because we can see when it gets stuck in the wheels, left behind on the floor, stuck in the gaps, or skipped over completely.

Hoover Blade+ vacuuming cereals off linoleum floor

Using large cereal shapes we can see how vacuums cope with larger pieces of debris like crumbs and small stones. Some vacuums push the cereal around, crush it up, or simply can’t cope, so this is a good hurdle for a vacuum to jump over.

Testing hair on linoleum with the Dyson Cyclone V10 Absolute

Hair and pet fur can be the greatest challenge for a number of vacuums. They're either missed entirely, or get tangled in the rollers. Clearing out tangled hair is never a pleasant job. We scatter hair extensions across linoleum, hard floor, and carpets. Some vacuums need a lot of help collecting the hair, others need only a little. When we test, it’s easy to see which is the best, because it’s the one we will reach for to clean up the mess that the others cannot.

Specialist pet hair vacuums often have removable rollers or parts of the floorhead. After vacuuming, we test how well these rollers can be removed and how much better that makes the hair removal process.

The Dyson Cyclone V10 Absolute accessories out of the box on test

Where there’s a special setting, we have a special test. Some vacuums have extra features, tools, and settings and we want to ensure that these aren’t marketing gimmicks. We’ll use these appropriately on different floor types and scenarios and gauge how well they perform.

Dyson Ball Animal 3 review

Vacuums are every cleaner’s best friend, until you have to clean or empty the vacuum yourself. This is the tipping point: your vacuum could redistribute all of the mess that you’ve carefully cleaned up, or it might effortlessly empty away.

Some vacuum cleaners have bags, which seal and filter dust, helping those who suffer from allergies. Bagless vacuums can be a little more messy, so we are careful to test the bin emptying aspect. At this point, we will also think about storage. It’s great to have lots of accessories, but if that makes the vacuum fiddly to store, you’d want to know. Equally, some vacuum cleaners can be disassembled and stowed away, whereas others will need a big cupboard or wall mount to store as a pre-assembled vacuum.

We take the entire vacuum cleaning experience and weigh that against the cost and warranty of the vacuum. If it's affordable and impressive, it’s sure to be on our best vacuums roundup. If a vacuum has a short guarantee, is expensive, or doesn’t deliver on promises, we will take that into account. If a vacuum is cheap, but suffers in power, performance, and capacity as a result, it will be marked down too.

Our team of testers is well acquainted with all the good, the bad, and the ugly (but sometimes brilliant) vacuums on the market. At this point, we draw on this knowledge network and try to take an objective step back. However, it’s also an opportunity for us to weigh in and offer you some personal experience and insight. It’s at this point that we will tell you who this vacuum would suit, who it wouldn’t, and we might send you in the direction of another appliance. For example, here's where we might make a call on which best between Shark vs Dyson,

I’m a driving expert – here’s how TikTok could help you pass your driving test first time and save you HUNDREDS

A DRIVING expert claims that TikTok could help learners to pass their driving test first time, and save them a huge amount of cash.

With the test backlog caused by the Covid-19 lockdown still ongoing, learners who fail their driving exam face waiting months for a new test date. 

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A new survey by driving experts Vanarama found that one in eight drivers (12%) prioritises theory and practical driving test revision over academic exams such as A-levels and university exams. 

A further one in five (21%) of drivers said they revised the same amount of time for their theory and practical driving tests and A-levels and university exams.

Handily, they have provided five tips to help you pass your driving test the first time.

In 2022, people in the UK spent, on average, 27.18 hours on TikTok per month, according to research from Statista.

Many driving instructors upload TikToks of their students' mock exams and lessons for people learning to take tips from - so get watching now to give yourself a better chance of passing first time.

It can be tempting to book a practical test in an area you’ve never even been to before, never mind having driven there, just so you can secure the earliest date possible.

However, this could hinder your chances of passing first time.

Not only will it add to nerves, but it’s an advantage to know the driving test routes before taking your practical.

It can be tempting to glance at your examiner whilst taking your practical driving test to try and gauge what they’re thinking and noting down. 

However, this could result in you failing your driving test for not concentrating on the road, which could, in turn, cause you to veer off track and potentially cause an accident. 

Your nerves will most likely be running high throughout your practical exam, so if you mishear or aren’t sure what the examiner has asked you to do, don’t be afraid to ask them to repeat.

Overthinking and being self-critical in your practical test will cause you more harm than good.

Sometimes you can be aware of a driving mistake you have made straight after doing it and assume you’ve failed your test, causing you to take the rest of the test less seriously and make further errors.

This comes after a driving instructor revealed the three things you didn't know are illegal on the roads.

Plus, a driving expert has revealed why drivers don't need to stop at all red lights.