Drug Development

#AACR17 roundup: Bristol-Myers, Merck KGaA and Pfizer in the spotlight, marking progress with checkpoints

PHOTO: © AACR/Todd Buchanan 2017


Julie Brahmer, Johns Hopkins

Bristol-Myers IDs a subset of patients who see a durable, 5-year response to Opdivo

Washington, DC — Now that the first wave of PD-1 checkpoint inhibitors have been in use for awhile, we’re starting to see just how durable they can be for some patients. In an update on Opdivo at AACR, Bristol-Myers Squibb reports that they tracked a 5-year survival rate of 16% for patients with advanced cases of non-small cell lung cancer.

Based on historical data, Bristol-Myers says that patients in that category once could only expect a survival rate of less than 5%.

“This is the first report of the long-term survival rate in patients with metastatic NSCLC treated with an immune checkpoint inhibitor. Our study results show that for a small subset of patients, immunotherapy can work for a very long time,” said Julie Brahmer, associate professor of oncology at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins.

Fouad Namouni, Bristol-Myers Squibb

What distinguishes these patients?

Bristol-Myers Squibb’s Fouad Namouni, who runs the oncology development group, tells me that they’re still working on that, trying to understand the biomarkers that could flag which patients are most likely to get the most durable responses. One likely answer, he notes, is that the patients with the most inflammatory tumors, with the largest mutation burden, could be benefiting disproportionately.

More mutations, he says, means that the tumors become “more visible to the immune cell,” targeting them for destruction.

Pfizer, Merck KGaA spruce up Bavencio’s profile with a data update

Howard Kaufman, Rutgers

Merck KGaA and its partner Pfizer turned up at AACR over the weekend with some improved outcomes for their checkpoint drug avelumab, recently approved as Bavencio for rare cases of Merkel cell carcinoma.

Evidence of a slightly amped up and more durable response will help these new arrivals on the checkpoint scene make quick progress as it works its way into an increasingly crowded field. Starting with this rare form of skin cancer, they now have 30 trials underway in various indications, coming in behind Merck, Bristol-Myers and Roche.

AstraZeneca will be the next to arrive, as it leaps into a blockbuster field with durvalumab. And behind AstraZeneca lie a whole new wave of checkpoints that are being hurried along, as the pioneers start a slew of combination studies — as our latest story on the IDO1 combos indicate — to advance their work.

The researchers for these two companies reported that:

(A)fter longer follow-up, the number of patients to have a response increased to 29, for an overall response rate of 33 percent after a median of 16.4 months of follow-up. In addition, the number of patients to have a complete response increased to 10 because one of the partial responses had improved to a complete response, and another patient newly recorded to have a response had a complete response.

At the time of data cutoff, 21 of the responses were ongoing and the median duration of response had not been reached. The researchers estimated that 74 percent of patients will have a response that lasts one year or longer.

Merck KGaA sped through clinical trials in three-and-a-half years to get this first approval, a milestone that Pfizer helped make happen with a record $850 million upfront for its partnership arrangement with the German Merck, which has gone well over a decade without a blockbuster addition from its R&D ops.

Howard Kaufman, a surgical oncologist at Rutgers Cancer Institute of New Jersey, noted:

The findings of long-term responses and well-tolerated safety profile suggest that avelumab could be an important new agent for patients with Merkel cell carcinoma who have failed prior chemotherapy. Given these results, it will be interesting to determine whether response rates could be increased by giving avelumab prior to chemotherapy or in combination with other treatments.

Opdivo, Yervoy combo scores higher survival rate for melanoma, with worse adverse events

Bristol-Myers, which has been working on bolstering its case for a combination of Opdivo and Yervoy in treating cancer, also turned up at AACR with new data that highlights improved survival rates for melanoma rates.

James Larkin, Oncologist

Oncologist James Larkin and colleagues enrolled 945 first-line patients with advanced melanoma and randomly assigned them in equal groups to nivolumab plus ipilimumab, nivolumab, or ipilimumab.

After a minimum follow-up of 28 months, investigators reported, median overall survival among those patients randomly assigned ipilimumab was 20 months. The median OS had not been reached for the nivolumab plus ipilimumab or the nivolumab plus placebo arms.

A total of 64% in the combo arm achieved two-year survival, the highest rate. The rate was 59% and 45% among those randomly assigned nivolumab plus placebo and ipilimumab alone. But the combo arm also experienced worse adverse events.

Researchers added:

A similar trend was seen for median duration of response. Median duration of response had not been reached in the nivolumab plus ipilimumab arm, while it was 31.1 months and 18.2 months for the nivolumab plus placebo arm and ipilimumab alone arm, respectively. In descriptive analyses, meaning the study was not powered for this comparison, patients randomly assigned nivolumab plus ipilimumab had a 12 percent lower risk of death compared with those randomly assigned nivolumab plus placebo.

“It is exciting to see that initial results suggest that the nivolumab plus ipilimumab combination provides favorable survival outcomes compared with ipilimumab alone,” said Larkin. “However, the combination also results in a higher rate of severe adverse events than nivolumab or ipilimumab alone, so it is important to consider this when making treatment decisions for patients.”


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