The big headlines from the American Association for Cancer Research meeting in Chicago were all about the battle over the latest lung cancer data, and for good reason. Lung cancer remains the deadliest cancer, but the Phase 3 data suggest that treatment options for some of the direst cases could soon rapidly expand.
There were results from earlier stages of clinical studies and preclinical research, which is the traditional material for AACR, as well as a couple of late-stage letdowns that came to light. Here’s a sample of other cancer news blowing in the Windy City and beyond this week.
EARLY ON TARGET
Drugs designed to target specific mutations in particular types of cancer—HER2-positive breast cancer or EGFR-positive lung cancer, for example—have been around a long time, with most approved in the past two decades.
But the FDA gave the field a big jolt last year when it approved Merck’s pembrolizumab (Keytruda) to treat tumors with a specific genetic alteration regardless of origin—the first decision of its kind. Loxo Oncology (NASDAQ: LOXO) and Ignyta (NASDAQ: RXDX) are leading similar efforts and could have drugs on the market in coming years. Their commercial success will depend on whether DNA testing to find patients with more mutations, even rare ones, becomes more widely adopted (and reimbursed by insurance).
At AACR, Blueprint Medicines (NASDAQ: BPMC) of Cambridge, MA, provided a first look at human data for its BLU-667, which targets so-called RET fusions that can drive cancers of the lung, thyroid, and more. So far, 7 of 14 patients (50 percent) with non-small cell lung cancer and 10 of 25 (40 percent) with medullary thyroid cancer who have failed other drugs have responded to BLU-667.
Why is such an interim look noteworthy? Blueprint CEO Jeff Albers says the company will pursue “expedited development” of its drugs in genetically defined patient subgroups.”It’s early to speculate about an accelerated approval pathway,” Albers told Xconomy, but there’s precedent. Loxo filed for accelerated FDA approval based on three studies, totaling 55 patients with TRK fusions. Blueprint will see where it stands after adding more patients with different cancer types to the Phase 1 study and focusing more on how long their responses last, rather than just whether they respond at all. “Ultimately, our registration strategy will be guided by additional data from the ongoing trial,” Albers says.
Wall Street wasn’t impressed and sent Blueprint shares down 13 percent. Blueprint will soon face competition from Loxo, whose own RET fusion-targeting drug is in Phase 1. Albers, who notes Blueprint will test a higher dose of BLU-667 in further testing, brushed off the “day-to-day movements in the market.”
“We believe the data reported at AACR give us a very solid foundation to rapidly advance the program,” he says.
—Poseida Therapeutics released very early data from a Phase 1 study of its CAR-T cell therapy for multiple myeloma. The live T cells are drawn from a patient, engineered to target the protein BCMA, and infused back to the patient.
It’s only three patients on a low dose of cells, but San Diego-based Poseida said the results—activity against the cancer and no “cytokine storm” side effects that often come with CAR-T therapy—were good enough to step up to the next dose. Bluebird Bio (NASDAQ: BLUE) and Novartis (NYSE: NVS) have the most advanced CAR-T programs for myeloma, with Bluebird and partner Celgene (NASDAQ: CELG) planning a pivotal study this year. Poseida’s study is backed with a $20 million grant from California’s regenerative medicine agency.
—Checkmate Pharmaceuticals of Cambridge, MA, has nudged its way into the combination immunotherapy game with promising early data presented Monday. It’s well documented that checkpoint inhibitors only help a minority of patients. With its drug CMP-001 Checkmate wants to make resistant cancers vulnerable to checkpoint therapy. Its first test: CMP-001 and pembrolizumab in melanoma patients who are failing treatment with pembrolizumab.
The early numbers at AACR: 15 of 69 evaluable patients (22 percent) who had failed a median of two treatments, including checkpoint therapy, responded to the CMP-001-pembrolizumab combination. Six of the responses have lasted more than six months, and two have held up more than 84 weeks. The drug is being evaluated in multiple tumor types, not just melanoma. For people who don’t respond to checkpoint inhibitors in melanoma, nothing has proven effective, said CEO Art Krieg. “The FDA told me at a melanoma meeting that this is their position for this population, and that an effective therapy would be eligible for accelerated approval,” he told Xconomy.
—Tesaro (NASDAQ: TSRO) of Waltham, MA, presented the first human data for its checkpoint inhibitor TSR-042, which is being developed for solid tumors with a specific genetic defect known as microsatellite instability-high (MSI-H), which hobbles their ability to repair their own DNA. It’s the same target pembrolizumab was approved to hit in the historic FDA decision last year.
In the Phase 1 GARNET study, 7 of 15 (47 percent) of patients with endometrial cancers and 7 of 24 (29 percent) patients with non-small cell lung cancer responded to treatment. RBC Capital Markets analyst Kennen MacKay wrote that while the data are promising, they are “largely undifferentiated” from pembrolizumab, meaning a “competitive environment” looms if approved.
BAD NEWS IN PHASE 3
—Newlink Genetics (NASDAQ: NLNK) announced early Phase 1 data for its indoximod in brain cancer patients at AACR, but the bigger news came at the end of its press release. Ames, IA-based Newlink is shelving a Phase 3 melanoma study combining indoximod and checkpoint inhibitors pembrolizumab and nivolumab. Indoximod is an IDO inhibitor, a type of drug many companies hope to combine with checkpoint inhibitors to boost immunotherapy response rates. But Newlink is hitting the pause button after a similar effort in melanoma from rival Incyte (NASDAQ: INCY) failed a big Phase 3 trial. Newlink shares fell 16 percent Monday but recovered those losses Tuesday.
—The precipitous fall of Celldex Therapeutics (NASDAQ: CLDX) continues. Two years ago, the company’s cancer vaccine rindopepimut failed a Phase 3 study in brain cancer after encouraging early signs. Now the company is tossing glembatumumab vedotin after failing a mid-stage trial in breast cancer. Hampton, NJ-based Celldex plans to restructure and still has five drugs in clinical trials. But shares now trade at less than $1. They were worth over $30 during AACR three years ago.
Ben Fidler contributed to this report.
Image of acute myeloid leukemia cells courtesy of the National Cancer Institute.