Petosemtamab Receives FDA Breakthrough Therapy Designation: Head / Neck Cancers • Hacker News Board

Re: Petosemtamab Receives FDA Breakthrough Therapy Designation: Head / Neck Cancers

#11

Post by sam537 » Sun, May 19, 2024, 2:31 AM UTC

hiddencost wrote: post #2

I'm struggling to figure out what is being reported. They were mostly able to stop progression in 37% of their test cohort? "At a data cutoff of February 1, 2023, efficacy-evaluable patients treated with petosemtamab (n = 43) experienced an overall response rate of 37.2%" They discussed "progression free" survival, which seems to mean the condition didn't worsen.

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.

Re: Petosemtamab Receives FDA Breakthrough Therapy Designation: Head / Neck Cancers

#12

Post by sam537 » Sun, May 19, 2024, 2:33 AM UTC

adamredwoods wrote: post #6

hiddencost wrote: post #2

I'm struggling to figure out what is being reported. They were mostly able to stop progression in 37% of their test cohort? "At a data cutoff of February 1, 2023, efficacy-evaluable patients treated with petosemtamab (n = 43) experienced an overall response rate of 37.2%" They discussed "progression free" survival, which seems to mean the condition didn't worsen.

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 on…

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.

Re: Petosemtamab Receives FDA Breakthrough Therapy Designation: Head / Neck Cancers

#13

Post by sam537 » Sun, May 19, 2024, 2:35 AM UTC

adamredwoods wrote: post #7

Petosemtamab (MCLA-158) is an investigational IgG1 antibody targeting EGFR. 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/

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).

Re: Petosemtamab Receives FDA Breakthrough Therapy Designation: Head / Neck Cancers

#14

Post by refurb » Sun, May 19, 2024, 4:42 AM UTC

hiddencost wrote: post #2

I'm struggling to figure out what is being reported. They were mostly able to stop progression in 37% of their test cohort? "At a data cutoff of February 1, 2023, efficacy-evaluable patients treated with petosemtamab (n = 43) experienced an overall response rate of 37.2%" They discussed "progression free" survival, which seems to mean the condition didn't worsen.

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.