It's been awhile since I've posted on Hot Copper. To some, the...

It's been awhile since I've posted on Hot Copper. To some, the results may be underwhelming. I'm neutral at the moment and maybe a literature review might help put things in perspective. Best to emphasise this is early days given the Phase I study design - there are only six evaluable patients only based on the conference presentation.

I do find it strange that Imugene targeted metastatic triple negative breast cancer. I might be missing information about their study rationale but they might have preferred to address a gap in the research on treatment outcomes for which breast cancer that has spread.

Here's a summary below. Metastatic disease is extremely difficult to treat and thus, the responses or lack therefore in CheckVacc (kind of) don't surprise me. There's more combination studies out there but I don't have time to look at them all. What's clear is that metastatic breast cancer has poor treatment outcomes. Note that CheckVacc includes patients who have received prior lines of chemotherapy so they have probably been heavily pre-treated.

For those who want to see a consolidation of the evidence so far on immunotherapy for triple-negative breast cancer - see https://link.springer.com/article/10.1007/s10549-022-06665-6.

In short, I think this study is highly restricted (metastatic, heavily non-responsive to chemotherapy) plus a very small sample for the time being. DYOR.

Imugene's preclinical trial on CF33-hNIS-anti-PD-L1 on breast cancer in mouse

Their preclinical trial (Chaurasiya et al., 2020) didn't examine how CF33-hNIS-anti-PD-L1 on metastatic breast cancer in a mouse model. It did indicate anti-tumour efficacy but again, it seemed like it wasn't for metastatic disease.

Phase III on pembrolizumabfor metastatic triple-negative breast cancer

Winer et al. (2021) studied pembrolizumab (Keytruda) versus investigator-choice chemotherapyfor metastatic triple-negative breast cancer in a large Phase III study. Larger sample and still poor results for response. Imugene's combination developmental drug didn't result in any responses but again, I think this is due to the small Phase I trial and the notorious challenge of treating metastatic disease.



Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer

Vinyak et al. (2019) studied a combination of niraparib and pembrolizumab (Keytruda) for advanced or metastatic triple-negative breast cancer. There's no response rate for specifically the metastatic patient cohort. However, the objective response rate (ORR) was 21% (5 CR; 4 PR) in a sample of 47 evaluable patients. Again, larger sample than the CheckVacc study. It's also not clear whether the responses were for patients without metastatic disease.