AACR recap: IDOs under the microscope
Over the past week, more than 20,000 cancer researchers, clinicians and biopharma insiders poured into Washington, D.C. for the 110th annual meeting of the American Association of Cancer Research.
The five-day conference highlighted the excitement surrounding immuno-oncology, advances in targeted therapy and emerging technologies like liquid biopsies — developments that have sparked a flood of industry investment and portfolio reshuffling to focus on the elusive disease.
While AACR's program covered an enormous breadth of research (the conference guide alone stretched to 211 pages), two areas stood out: new combination therapies showed some promise and clinical data sketched out early hints at a long-term benefit from cancer immunotherapy for certain patients.
With approval of Pfizer and Merck KGaA's Bavencio (avelumab), there are now four checkpoint inhibitors licensed in the United States with others advancing through clinical development. The new class of immunotherapies has spurred hope of moving the needle in treatment of certain cancers. Yet, only certain patients see a meaningful benefit from the drugs and it's still not clear how best to identify the patients most likely to respond.
In response, pharma and biotech companies up and down the industry have begun testing checkpoint inhibitors in combination with other drugs, hoping to boost efficacy and broaden benefit.
At AACR, several companies presented data on a type of immunotherapy that inhibits the IDO signaling pathway. Like a PD-1 or CTLA-4 blockade, blocking the IDO pathway is thought to help unleash a patients immune system to better target and attack cancer cells. IDO refers to an intracellular enzyme that modulates immune response and can be co-opted by tumors to evade detection.
Incyte Corp. has been testing its IDO1 inhibitor epacadostat in combination with checkpoint inhibitors and had already signed collaborations with Merck & Co., Bristol-Myers Squibb, Roche and AstraZeneca.
During AACR, though, the Delaware-based biotech accelerated its work with Merck and Bristol-Myers, announcing new plans for late-stage testing of combinations pairing epacadostat with each company's respective checkpoint inhibitor.
The new agreements put Incyte out in front in the IDO space and, by betting on both Merck's Keytruda (pembrolizumab) and Bristol-Myers' Opdivo (nivolumab), the biotech is well placed to take advantage of whichever combination shows the most promise.
NewLink Genetics, though, is on Incyte's heels and revealed interim Phase 2 results showing a combo of its IDO pathway inhibitor indoximod and Keytruda led to a 52% response rate among patients with advanced melanoma. While markets reacted negatively, the data measured up to results seen in a previous study of Keytruda monotherapy and NewLink plans to push quickly into Phase 3.
Explaining the excitement around IDO, NewLink CEO Charles Link said the data suggested IDO could be a potentially less toxic replacement to CTLA4 inhibitors in immuno-therapy combinations.
Elsewhere, survival data for Bristol-Myers' Opdivo, Roche's Tecentriq (atezolizumab) and Pfizer's Bavencio (avelumab) fit new puzzle pieces into the emerging picture of checkpoint inhibitor's longer term benefit.
Clinical data for Opdivo suggested the drug delivered a durable long-term benefit for some patients with advanced melanoma and non-small cell lung cancer (NSCLC).In advanced melanoma, for example, 64% of patients who received a combination of Opdivo and Bristol-Myers' older immunotherapy Yervoy (ipilimumab) were alive after two years.
Investigators also presented follow-up data from an early, small Phase 1b study of Opdivo in second-line advanced NSCLC that showed 16% of patients were alive after five years — the longest survival follow-up available for a checkpoint inhibitor in that type of lung cancer.
More than half of patients with Merkel cell carcinoma treated with Pfizer's Bavencio in a Phase 2 trial were alive after one year — data that helps back up the drug's recent approval in that indication.
As for Roche's Tecentriq, data from a Phase 1 clinical study in triple negative breast cancer showed the checkpoint inhibitor helped a small group of patients live past two years.
All of these data points are in different groups of patients and show mixed signals that still need to be explored, but as the checkpoint inhibitors currently on the market mature, overall survival data will be increasingly important to evaluate the benefit of using immuno-oncology monotherapy over time and to evaluate the best approach for future combinations.
- BioPharma Dive AACR: Incyte hedges bet on combo strategy
- BioPharma Dive AACR: NewLink's IDO data shows promise, but is it enough?
- BioPharma Dive AACR: Busy start for Bristol-Myers Squibb's Opdivo
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