Surprising and market-moving information often comes out of the annual American Society of Clinical Oncology (ASCO) meeting, and so far, ASCO18 hasn't disappointed. From bluebird bio's (BLUE -1.07%) great-but-not-good-enough results in multiple myeloma to Loxo Oncology's (LOXO) stellar results in RET-fusion cancers to Nektar Therapeutics (NKTR -2.22%) head-scratching data, here are some quick takes on the data released this weekend.
Sky-high predictions missed, but a win nonetheless
One of the most highly anticipated presentations was the update from co-developers Celgene (CELG) and bluebird bio on bb2121, a BCMA targeting CAR-T for multiple myeloma.
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As a refresher, bluebird bio was a big winner at ASCO17 because of bb2121 delivering a 100% overall response rate in a small group of heavily pretreated multiple myeloma patients. The data was updated in December to include more patients, and at that point, overall responses were still 94% -- a remarkable achievement for these patients given they've all failed on a median seven prior treatments.
At ASCO, industry-watchers were hoping that the latest data would show progression-free survival (PFS) as high as 15 months. They didn't get what they wanted. Instead, PFS came in at 11.8 months, or just under the anticipated 12-month to 15-month range.
The knee-jerk reaction to the data was a post-market 5% sell-off in shares, however, investors might not want to be too pessimistic. The response rates and PFS data trounce anything seen in this patient population before and there's nothing in the data yet that has me worried about bb2121's chances at eventual FDA approval. Overall, a bit of long-term perspective might be warranted. After all, this is a megablockbuster indication, there's a huge unmet need for new fourth-line and up treatment options, and an FDA filing for approval could come as soon as next year.
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Another win for this up-and-coming cancer company
Loxo Oncology's shares have soared since data for larotrectinib in TRK-fusion cancers wowed the industry at ASCO in 2017. At ASCO18, the company's doing it again with better-than-expected overall response rates for a second drug, LOXO-292, that targets "rearranged during transfection" (RET) fusion cancers.
In May, the ASCO18 abstract for LOXO-292 showed a 69% overall response rate (ORR), but those results were from a cut-off date in January. This weekend, the company presented maturing data that show ORR improved to 77%.
Those results suggest that LOXO-292 could be a major advance for RET-fusion patients. RET-fusions aren't common, but they still represent thousands of people per year in the United States. For instance, about 2% of non-small lung cancer patients (NSCLC) harbor RET-fusions and that works out to 4,600 patients in the U.S. alone. The drug delivered a lower ORR in medullary thyroid cancer (MTC), but it was still a very solid 45%. About 60% of MTC patients have RET-fusions, so that adds another 3,000 or so addressable patients.
The big thing to watch this week will be how investors view Loxo's results in comparison to results presented earlier this year by Blueprint Medicines (BPMC 0.59%). Blueprint's BLU-667 also targets RET-fusions and at the American Association for Cancer Research meeting in April, Blueprint revealed a preliminary overall response rate of 50% for NSCLC and 40% for MTC. It's bad science to compare unrelated trials, so investors might be best off viewing Loxo and Blueprint's data as evidence that they're both working on a winning approach.
A new approach to catching cancer early
Perhaps, one of the most-surprising winners at ASCO18 will be Grail, the venture-backed start-up born out of DNA-sequencing giant Illumina (ILMN -1.35%) that's attempting to detect cancer early on by using a blood test.
At ASCO, Grail said it was able to spot cancer in about 40% of patients with early stage lung cancer and 90% of patients with late-stage lung cancer. Those results are from a relatively small 127-patient group, but Grail's research involves thousands of patients, and over time, the company hopes its algorithms will improve and its detection rates will climb.
A lot of people think Grail may succeed. It's already raised $1.6 billion in venture funding from luminaries including Microsoft's Bill Gates and Amazon's Jeff Bezos. But we're still miles away from being able to spot cancer in otherwise healthy people early on when it's easiest to treat.
Ultimately, industry watchers would like to see 80% plus detection rates in early stage cancers and very few false positives. Currently, false-positives are happening at a rate of between 1% and 2% and while that may not sound very high, it translates into millions of people across the entire population.
Nevertheless, Grail's ASCO insight confirms that its tests can spot tiny DNA fragments in the blood cast-off by cancer cells, and that's a big step in the right direction in its quest.
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Nektar's data raises questions
Data for NKTR-214 when used alongside Bristol-Myers Squibb's (BMY 0.96%) PD-1 checkpoint inhibitor Opdivo was so good last year that Bristol-Myers inked a megadeal to acquire shared rights to the drug a few months ago.
Over the weekend, Nektar Therapeutics presented updated data on NKTR-214 that sparked debate between those who were impressed by improving response rates over time and those who were concerned by lackluster response rates in recently enrolled trial patients.
In November 2017, the overall response rate to NKTR-214 plus Opdivo in efficacy-evaluable treatment-naive melanoma patients with melanoma was 64%. At ASCO, data showed that the ORR in the first subset of patients improved to 85%, or 11 of 13 patients. However, when you include patients more recently enrolled, the ORR falls to 50%, or 14 of 28 patients. Back-of-napkin math shows that just three of the 15 newly enrolled patients responded as of the data cut-off.
The situation was similar in kidney cancer. Initially, the response rate to NKTR-214 plus Opdivo was 46%. However, the ORR has improved to 64% for those patients based on the ASCO presentation. If you include newly enrolled patients, though, the ORR falls back to 46%.
Make no mistake, these are still great response rates. But, bears will maintain that response rates could fall further as more patients are enrolled. Bulls will counter by arguing that tumor responses improved over time for the first subgroup of patients, and that the same will happen in the second subgroup, too.
Ultimately, only time will tell just how active NKTR-214 is, but one important takeaway for investors is that NKTR-214 appears to make Opdivo work better in PD-1 positive patients and in PD-1 negative patients who don't normally respond to it and as a result, Bristol-Myers and Nektar plan to advance their combo drug into phase 3.
