The American Society of Clinical Oncology annual meeting, the world’s largest cancer conference, wraps up today in Chicago. Investors have dissected the data, picked winners and losers, and sent some biotech stocks soaring and others tumbling.
In the days before ASCO, Xconomy previewed two major themes: the feverish and flawed race to develop cancer immunotherapy combinations, and the progress of “tissue agnostic” cancer drugs, the advanced guard of precision medicine.
Today, we’ll wrap up the ASCO headlines that hit on those themes and bring you other news from the meeting. Read on for details.
COMBO FEVER: NEKTAR’S CYTOKINE STORM
Heading into ASCO, Xconomy published a story about the rise and fall of IDO inhibitors, and the lessons the story might provide for the next ‘can’t miss’ immunotherapy combinations. One takeaway: data from early, uncontrolled trials of these combinations can be misleading, particularly in cancers where a class of FDA-approved immunotherapies, known as checkpoint inhibitors, already help.
Data released this weekend from Nektar Therapeutics (NASDAQ: NKTR) show that investors have become more skeptical of combination results in a post-IDO world. Big Pharma has shown interest in teaming a checkpoint inhibitor with synthetic versions of proteins called cytokines, as two recent billion-dollar deals from Bristol-Myers Squibb (NYSE: BMY) (with Nektar) and Eli Lilly (NYSE: LLY) (with Armo Biosciences) show.
For $2 billion, Bristol has bet that Nektar’s NKTR-214 can help more people respond to its immunotherapy nivolumab. The collaborators are launching several large Phase 3 combination trials in melanoma, kidney, and bladder cancer to test the theory.
At ASCO, Nektar and Bristol provided the latest look from an early study, PIVOT, that will set the stage for those big tests. They reported 11 of the first 13 melanoma patients responded to nivolumab/NKTR-214 combination, but then only 3 of the next 15. Among kidney cancer patients, 7 of the first 11 responded, but then only 5 of the next 15. Bristol and Nektar pointed to the combo’s activity in patients who have none of the protein PD-L1 on their tumors and tend not to respond to checkpoint blockers. They also noted the combo’s track record of delayed response in early testing, suggesting perhaps those numbers get better with time. Investors weren’t so sure: Nektar shares fell 39 percent, and Bristol shares slipped 4 percent. Here’s more from STAT.
PRECISION STEPS FOR LOXO, NCI MATCH
The FDA has approved only one cancer drug that targets mutations in a tumor, regardless of the tumor’s location or origin. But other so-called “tissue agnostic” drugs continue to advance, as does the massive NCI Match trial trying to prove the worth of precision cancer treatments.
Loxo Oncology (NASDAQ: LOXO), one company paving the way, now has two tissue agnostic cancer drugs that have shown promise in clinical testing.
Loxo said this weekend that 30 of 39 patients on its experimental LOXO-292 have responded to treatment, meaning at minimum their tumors shrank. These patients have tumors that formed in either the lung, thyroid, or pancreas, all driven by a specific genetic alteration known as a RET fusion. Loxo separately reported that 10 of 22 patients with medullary thyroid cancer, a rare type of thyroid cancer caused by a RET mutation, have also responded to treatment.
The news helped drive shares of Blueprint Medicines (NASDAQ: BPMC), which has a rival drug, down 9 percent. The data also put LOXO-292 on a potentially similar path to Loxo’s larotrectinib, a drug for another tumor alteration, TRK fusions. Even with only 55 patients spanning 17 cancer types in its data set, Loxo has asked the FDA to approve larotrectinib. A decision should come by late November. As Xconomy reported last week, larotrectinib is an important test case for the FDA and, if it’s approved, for insurers. Blueprint, Ignyta (NASDAQ: RXDX), and others following in Loxo’s footsteps will be watching.
The National Institutes of Health is also studying tissue-agnostic cancer treatments with the sprawling NCI Match trial that began in 2015. NCI Match produced its most significant update yet at ASCO, with results from three of its 40 treatment arms.
Among 65 patients with PIK3CA mutations, for example, the experimental Roche drug taselisib didn’t lead to any responses—though for 24 percent of patients, tumors didn’t spread for at least six months. (Roche said separately this weekend it is scrapping taselisib.) Just three of 37 patients with HER2-expressing tumors responded to the Roche cancer drug ado-trastuzumab emtansine (Kadcyla). Five of 50 patients with FGFR mutations responded to AstraZeneca’s experimental AZD4547.
Those numbers look underwhelming, but the NCI said in a statement that many of these patients have failed at least three therapies. The results are thus “particularly encouraging [and] suggests that future studies in populations with earlier-stage disease could potentially see more responses,” the NCI argued.
More results from the study, which is taking place at over 1,100 cancer centers, will come as the data mature.
NO CHEMO FOR SOME EARLY BREAST CANCER
Women with early-stage breast cancer might be better off without chemotherapy, according to a long-term study known as TAILORx. Funded by the National Cancer Institute, the study enrolled more than 10,000 women in six countries with hormone receptor-positive, HER2-negative, axillary lymph node-negative cancer, which accounts for about 70 percent of all breast cancer, according to the NCI.
Women who tested for intermediate risk of recurrence were randomly assigned to two groups. One group received hormone therapy alone, the other group received hormone therapy plus chemotherapy. The outcomes for the two groups were nearly identical at five years and nine years after treatment.
The study authors believe the new data suggest chemotherapy may be avoided in about 70 percent of women with this type of breast cancer.
Genomic Health (NASDAQ: GHDX), whose Oncotype DX genetic test was used in TAILORx to assign women a risk score, saw its shares rise 23 percent Monday.
THE NEXT FRONTIER FOR CAR-T
In the field of live T-cell immunotherapy known as CAR-T, one promising area of therapy is multiple myeloma, the third most common blood cancer in the U.S. After an early headstart, Bluebird Bio (NASDAQ: BLUE) remains the farthest along, ahead of Novartis, Nanjing Legend, and others, and is helped by its larger partner Celgene (NASDAQ: CELG). Bluebird reported the latest Phase 1 data from its experimental bb2121 product, which is initially being tested in patients who have failed to respond to several other treatments, including stem-cell transplants and some of the latest approved drugs.
On average, the 22 patients in the trial lived nearly a year—11.8 months—before their myeloma worsened. Bluebird and Celgene continue to expand enrollment, and with Phase 3 results hope to ask for regulatory approval for bb2121 next year.
BB2121 is engineered to recognize and attack myeloma cells with the protein BCMA, but Bluebird CEO Nick Leschly said the treatment seemed to work no matter how much BCMA was present on a patient’s tumor cells. (CNBC has more on the data here.)
LUNG CANCER SHOWDOWN
In the fast-moving field of lung cancer, immunotherapy—in combination with other drugs and on its own—has been changing the state of care for a few years now.
Earlier this year, Merck (NYSE: MRK), Bristol, and Roche each detailed data from combination regimens on newly diagnosed advanced lung cancer patients. Merck’s regimen of pembrolizumab (Keytruda) and chemotherapy is in the lead as the only immunotherapy approved as a first-line treatment for all non-small cell lung cancer patients. As Xconomy reported, lung cancer experts are scrambling to understand how each regimen might be best deployed.
ASCO provided a few new tidbits. In a closely watched Merck study called Keynote-042, encouraging topline results from a few months ago yielded to a more complicated picture. Used alone, pembrolizumab is already approved for NSCLC in patients who have high levels (more than 50 percent) of the protein PD-L1 on their tumors. Merck would like to expand the label to patients with lower levels of PD-L1, but the new Keynote-042 data “show some of the inconsistencies we’ve seen” with other immunotherapies in first-line lung cancer, wrote ISI Evercore analyst Umer Raffat in a research note.
For instance: Patients on pembrolizumab whose tumors produced at least 1 percent PD-L1 lived a median of 16.7 months, compared to a median of 12.1 months for chemo patients. Among these patients, pembrolizumab reduced the risk of disease worsening or death by 19 percent, compared to chemo. But for only those whose PD-L1 levels are between 1 and 49 percent—the group pembrolizumab monotherapy isn’t approved for—the risk of disease worsening or death was cut by only 8 percent.
Merck also detailed the results from Keynote-407, which tested pembrolizumab and chemotherapy in patients with the aggressive squamous form of NSCLC. Raffat noted that the regimen worked “across PD-L1 status,” and while caveats apply, appears to compare favorably to Bristol and Roche combination regimens for squamous patients. Pembro-chemo cut the risk of death by 36 percent in all patients, and by 39 percent in patients whose tumors didn’t express even 1 percent PD-L1.
Bristol, meanwhile, added new details from the Checkmate-227 study of nivolumab and its other FDA-approved immunotherapy, ipilimumab (Yervoy). Among the new insights: How patients in the study with different TMB or PD-L1 levels fared, and more granular details about nivo-ipi’s effects versus a nivo-chemo regimen. And Roche added data from IMpower131, another immunotherapy-chemo combination, meanwhile, which cut the risk of disease worsening or death by 29 percent. Still, Jefferies analyst Ian Hilliker noted last week that Merck’s regimen, which cut the risk of death in half, has “set the efficacy bar.” For Roche to directly compete, a better comparison might be Roche’s IMpower132, which tests atezolizumab with the same chemotherapy used in Merck’s regimen.
Merck shares climbed 2.4 percent on Monday.
—Shares of Waltham, MA-based Deciphera Pharmaceuticals (NASDAQ: DCPH) climbed nearly 48 percent after releasing data from a Phase 1 study testing experimental DCC-2618 in patients with gastrointestinal stromal tumors who have failed at least one treatment. (Blueprint Medicines is also developing a drug for GIST.)
—Jounce Therapeutics shares plummeted 33 percent on early data from a study testing its experimental JTX-2011 both as a monotherapy and in combination with Bristol’s nivolumab.
Alex Lash contributed to this report.
Photo of Chicago skyline by Tony Webster via a Creative Commons 2.0 license.