Spectrum Pharmaceutecals Inc (SPPI)

[antihama]

The AACR 2019 Pozi recently released abstract had me thinking about the pozi-TDM1 P1 trial that stopped recruiting patients. My guess as to why was that perhaps they were seeing toxicity. I know others were thinking they were moving on from mBC which I don’t espouse to (yet) but we’ll definitely know more by the end of the year if true (if we don’t hear anything by SABCS that will speak pretty loudly too since the SPPI mBC posi trial has mature data.

Note- The SPPI mBC posi trial dosed patients at 2x the amount as the counterpart Korean trial which was looking to see 4.5m PFS as opposed to Standard of Care of 3.3 months (see post 1743) but got PFS 4.04 months, DCR 75.49%, ORR 18.8%.

But I digress, getting back to the pozi-TDM1 combo, perhaps they stopped recruiting because they were seeing efficacy at the low doses and they have a combo trial mapped out for the 2nd half? Anyhoozle, the pre-clinical data in this abstract is pretty intriguing. It would be a shame if they stopped because of toxicity. From the abstract

…Lastly, in a HER2 mutant NSCLC PDX model (HER2 Y772dupYVMA), the combination of low dose poziotinib (2.5 mpk) & a single dose of TDM1 (10mpk) resulted in complete tumor regression in 9/9 mice, compared to 2/9 mice receiving TDM1 alone or 0/9 mice receiving low dose poziotinib (p<0.0001). In conclusion, HER2 exon 20 insertions & L755P mutations are resistant to the majority of HER2 TKIs, but remain sensitive to poziotinib. Combination of low dose poziotinib & TDM1 caused complete tumor regression in a HER2 exon 20 mutant PDX model. These data suggest that poziotinib alone & in combination with TDM1 has activity against the most common HER2 variants across diverse malignancies & that clinical studies testing these agents in HER2 mutant cancers are warranted.

https://www.abstractsonline.com/pp8/#!/6812/presentation/2980