DR KROP: T-DM1 is a new agent for this type of breast cancer. It’s kind of a novel concept. It’s what’s called an antibody-drug conjugate. It’s taking the trastuzumab HER2-directed antibody and very stably linking a very potent cytotoxic agent to that antibody, with the idea that the antibody is able to specifically deliver this cytotoxic agent, the DM1, directly to the cancer cell.
This is a drug that was tested in the Phase I population, starting at around 2006. It showed pretty significant activity in patients who progressed on multiple lines of therapy. And subsequently, there’s been two Phase II studies, both in patients who progressed on multiple lines of prior therapy, showing that this is an active drug with response rates in the 30 percent range.
And we have data that was presented recently at ESMO that looked in the first-line setting comparing a standard — again, docetaxel/trastuzumab versus T-DM1 as a single agent — and T-DM1 showed comparable response rates and actually an improvement in PFS — essentially the exact same hazard rate as we saw in CLEOPATRA, so about a hazard rate of 0.6 favoring T-DM1 against the docetaxel/trastuzumab. And it does that with also the additional benefit of significantly less toxicity. The Grade III adverse events were almost half in the rate of the chemotherapy with T-DM1.
DR HAYES: When I was a fellow, maytansine was going to be the cure for cancer.
DR LOVE: Really?
DR HAYES: It knocks out all the cell lines in the 40-cell panel that is at the NIH — I mean it’s an unbelievably powerful drug. But in the Phase ones, it’s also unbelievably toxic. And I think after the first three patients it was sent back to the NCI and said, you should have put it in mice first or something because this thing is…
And so, to me — I heard about this drug four or five years ago, but to me, the linker here is just brilliant. I mean I think this should be the invention of the year, or whatever, to figure out how to stick this drug to an antibody with no toxicity until it gets inside the cell. Because maytansine by itself is ungivable in terms of all kinds of toxicities but especially bone marrow toxicity. It’s really tough. So this is, I think, just unbelievably impressive.
DR VOGEL: I was on the Phase I working group when maytansine was —
DR GONZALEZ-ANGULO: Shelved.
DR VOGEL: — in development, and it didn’t stay there very long.
DR HAYES: But you remember it was going to be the cure for cancer.
DR VOGEL: Yeah.
DR HAYES: I mean you — I remember Dr Frye —
DR VOGEL: Incredibly potent drug.
DR HAYES: Dr Frye was so excited about this drug, and boy, it just…
DR KROP: So actually, your clinical experience is certainly consistent with the preclinical data, but actually if you compare it head to head in vitro it’s up to a thousand times more potent than Adriamycin® —
DR HAYES: Yes.
DR KROP: — it’s up to 500 times more potent than paclitaxel.