Between September and January, however, the tumors in my neck shrank by about 20%, which is a startingly good response by R / M HNSCC standards.
Perhaps the most interesting question will ultimately be whether oncologists prescribe petosemtamab for patients who get early clean surgical margins, in an effort to prevent recurrence. Oncologists are reluctant to impose chemo-radiation because of chemo's deleterious side effects, but petosemtamab, though it causes rashes, paronychia, and other skin problems.
You should check out a currently approved drug that is very similar called amivantamab (Rybrevant). Also targets EGFR and MET (MET can sometimes be a resistance mechanism to EGFR blockade).
Efficacy usually drops off a cliff after first line (first therapy) treatment in many cancers. The best chance of being cured is typically the first therapy.
This is a population who has already been treated with a PD-1 (or PDL-1) therapy and platinum chemotherapy, which is pretty much the best treatment available, and their cancer has come back.
ESMO (European) guidelines suggest "Taxane or methotrexate or cetuximab or BSC (best supportive care)" for these patients.
Median OS for this drug was 11.5 months while the KEYNOTE-048 trial had the current standard of care at 10.7 months. So this drug is at least as good as current therapy which is very promising in such a small trial and difficult to treat population.
Which is good numbers in the cancer treatment arena.
>> “We look forward to continued constructive conversations with the FDA as we move forward in our plan to initiate a phase 3 trial in previously treated HNSCC mid-2024 and prepare for a potential phase 3 trial evaluating the combination of petosemtamab and pembrolizumab [Keytruda] in previously untreated patients."
I understand the caution, but I firmly believe oncologists need to get more aggressive with multi-line treatments.
The problem here is the potential toxicity of this combination.
In lung cancer for example, the combination of anti-EGFR therapy + pembrolizumab led to deadly pneumonitis (lung inflammation). We want to cure more patients, but we don't want to kill them before their cancer.
I’m not sure I agree that conservatism treatment by oncologists is holding back cancer cure. Maybe in some cases but in others… eg multi-drug regimes like FOLFIRINOX, where cancer patients routinely choose hospice over treatment because of its toxicity and meager benefit. Or even more cutting edge drugs like ENHERTU, which has shown striking benefits for some, but something like 15% of patients have to be pulled off treatment due to intolerable toxicities, and twice that amount have serious adverse events and occasional patients die (“grade 5 to x”)
I agree there is much work to do in cancer, and oncologist behavior is included in that. Simply getting more aggressive may help some but isn’t necessarily a magic bullet and has risks. (please pardon my emotional reaction to this)
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Maybe I can help.
Progression is usually defined by radiological endpoints (RECIST 1.1 criteria) meaning that at timepoint x the tumor stayed the same size, got smaller, or grew less than 20%.
Radiological measurement is very subjective so most of these trials centralize measurement of 'target lesions' (some patients have many tumors but not all are measured in clinical trials).
It is worth nothing that inside PFS not only progression is an event but also death. So if you progressed and/or died, you count as an event.
The overall response rate is a combination of complete response (tumor not measurable radiologically) and partial response (>20% reduction in size). That is a common trial endpoint.
As someone else said the Breakthrough designation is common and does not necessarily lead to efficacious drug approvals.
Yeah that’s all correct. It’s particularly notable because the study was a third line treatment. These patients had already progressed after taking a platinum based chemotherapy, which is a standard first treatment, and they also progressed after taking a PD-L1 immunotherapy. So these patients had very advanced and difficult to treat cancer. This represents a real improvement for them as they probably didn't have many options left outside very invasive surgeries or lots of radiation to the head and neck.
Also the treatment targets two cancer genes at the same time. The first is EGFR, which is a very well known therapeutic target. The second is LGR5, and I’m not as familiar with that one, but I think it might be a novel target for cancer. So that's important in that more drugs might target this gene or combinations of LGR5 and others and they might be more effective than this first effort.
"Breakthrough Therapy Designation" is a regulatory term. It's definitely good news, but it's also a pretty common occurrence that the FDA designates a breakthrough drug, and it does not guarantee that drug's ultimate approval.
It's also not really "news". It's a development that incrementally smoothes the path for what is still a highly uncertain outcome. And per the linked article it appears to be based on interim data in a phase 1/2 trial. Very early.
There are many drugs that look promising at this stage (that's why the breakthrough designation exists!) But this piece of news is unremarkable. Merus, the company behind Petosemtamab, alone has like seven cancer drugs in various stages of development.
And there are probably hundreds of cancer drugs in development at any given time.
So this is just a mechanical write-up of a regulatory checkpoint for a drug that's like 30% of the way to approval and is among many, many other cancer drugs all sitting at different points along the same continuum.
HN is really random, but also the submitter is an author whose posts are regularly submitted to HN and is a participant (I believe) in a trial for the drug in the article. The regular updates (and the author’s participation in threads) have endeared him to the community.
Merus's other trials (EGFR X c-MET) in NSCLC had serious side effects, but effective.
https://www.fiercebiotech.com/biotech/merus-shares-dip-inter...
Merus's pipeline, looks interesting:
https://merus.nl/pipeline/