If the annual meeting of the American Association for Cancer Research (AACR) in March put IDO inhibition on the map in immuno-oncology, next month’s mega-conference hosted by the American Society for Clinical Oncology (ACSO) could push interest even higher.
Shares of Incyte Corp. surged after clinical trial abstracts were posted online Wednesday, buoyed by positive signs of efficacy in a wide range of combination trials pairing its IDO1 inhibitor epacadostat with Merck’s Keytruda (pemobrlizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab).
Other combination approaches will be also be a key focus, particularly as other major players in immuno-oncology are positioning to challenge Merck’s early advantage with its Keytruda/chemotherapy combo in lung cancer.
With ASCO a little over two weeks away, here are seven highlights from the abstracts worth keeping an eye on:
As far as boosts to share prices go, Incyte came away looking the sharpest from Wednesday evening’s abstract release. The biotech’s stock jumped nearly 10% in post-market trading on positive signs of efficacy from its IDO1 inhibitor epacadostat in combination with Keytruda. (Shares opened Thursday up over 5%.)
In non-small cell lung cancer (NSCLC), treatment with the two drugs led to a 35% overall response rate in 40 previously treated patients who were evaluable for efficacy. In Merck’s Keynote-010 study, Keytruda monotherapy had notched an 18% ORR - suggesting a combination with epacadostat could deliver meaningful improvements.
Encouraging results were also seen in bladder cancer and squamous cell carcinoma of the head and neck, although data in heavily pre-treated triple-negative breast cancer and renal cell carcinoma looked less promising.
Merck had clearly seen enough evidence from the ECHO-202 study in the run-up to ASCO, expanding its collaboration with Incyte back in April to test the combo in five different tumor types across seven pivotal trials.
Not all watching were charmed, however. Piper Jaffray analyst Joshua Schimmer noted the response rates in solid tumors were generally in line with what would be expected from treatment with a PD-1 targeting monotherapy.
Also revealed on Wednesday were early results from a study testing epacadostat together with Bristol-Myers Squibb’s Opdivo (nivolumab). Bristol has a wide-ranging partnership with Incyte, reflective of the interest in combinations beyond CTLA-4 inhibitors.
More color on KEYNOTE-021
Merck bolstered its edge in first-line NSCLC earlier in May, winning U.S. approval of a combination therapy pairing Keytruda with the commonly used chemotherapy regimen of Eli Lilly’s Alimta (pemetrexed) and carboplatin.
Updated data in Merck’s abstract on the KEYNOTE-021 study show a slightly improved response rate of nearly 57% for the Keytruda/chemo arm, versus 30.2% for those receiving chemo alone.
Perhaps more interesting, the new data includes a hazard ratio of 0.69 for overall survival, which suggests a favorable trend in risk reduction despite crossover between the treatment and chemo arms. (The result was not statistically significant, but median OS still has not been reached in either arm.)
With approval as a combo in "all-comers" and as monotherapy in high PD-L1 expressors, Keytruda is clearly at an advantage in the lucrative NSCLC space - for now. AstraZeneca expects to read out data for its immuno-oncology combo in first-line around mid-year, and results from Roche’s IMpower150 could land as soon as the third quarter.
Monarch, but not king
New data from Eli Lilly’s MONARCH-2 study of its CDK 4/6 inhibitor abemaciclib suggest Pfizer’s Ibrance (palbociclib) may have yet more competition on its hands soon.
MONARCH-2 pits a combination of abemaciclib and fulvestrant against placebo plus fulvestrant in second-line treatment of women with HR+/HER2- advanced breast cancer.
According to an abstract posted Wednesday, median progression-free survival for the abemaciclib arm hit 16.4 months, compared to 9.3 months for the comparator arm. The improvement compares favorably with results from Pfizer’s PALOMA-3 study, although that looked at a slightly more advanced patient population.
Side effects, though, could hurt abemaciclib’s competitive profile. Nearly 9 in 10 patients experienced diarrhea, an adverse event Lilly has tried to mitigate with loperamide treatment.
Lilly plans to submit the MONARCH-2 data in the third quarter, following a New Drug Application based on another study later in the year.
Novartis, which recently won U.S. approval of its Kisqali (ribociclib), will also be presenting updated results at ASCO. Data from the abstract showed 54.7% of patients treated with Kisqali plus letrozole experienced progression-free survival through two years, compared to 35.9% of those receiving placebo plus letrozole.
CAR-T updates yet to come
Little new information was revealed Wednesday on CAR-T therapies, with Kite Pharma, Juno Therapeutics and Bluebird Bio all submitting previously released data in their abstracts.
Kite will be presenting updated results at the conference from its ZUMA-3 study of axi-cel in relapsed/refractory acute lymphoblastic leukemia – the same indication that Novartis is pursuing for its CAR-T therapy CTL-19, but in pediatric and young adult rather than adult patients.
Kite’s abstract for ASCO shows six of eight efficacy-evaluable patients achieved a MRD-negative complete response, with no cerebral edema reported. As disclosed in December 2016, one patient died from cytokine release syndrome related to axi-cel.
Juno, looking to reset from its failure with JCAR015, plans to unveil new data from its ongoing Phase 1 TRANSCEND study of JCAR017 in relapsed/refractory non-Hodgkin lymphoma. Look for increased patient numbers and longer duration of follow-up for both dose levels of JCAR017, which notched 80% overall response and 60% complete response rates back in December.
And in multiple myeloma, Bluebird Bio will be unveiling safety and efficacy results from an additional 9 patients treated with its anti-BCMA CAR-T therapy, known as bb2121. In November, the Cambridge biotech reported 100% of patients in its second and third dose cohorts saw a response, with two MRD-negative and another two in complete response.
Jitters on Newlink
While Incyte rose on market optimism around the potential of IDO inhibition, those high expectations didn’t help Newlink Genetics.
Shares in the Iowa-based biotech fell by more than 10% Thursday morning, a reaction to tepid results from a combo of its IDO1 inhibitor with Roche’s Tecentriq (atezolizumab).
Early data from a Phase 1b study across multiple advanced or metastatic solid tumors showed the combo led to partial responses in only 9% of the 45 evaluable patients. Eleven patients had stable disease.
Plans for this study involve disease-specific expansion cohorts, so more data will likely paint a clearer picture of the combo’s potential in individual cancers. But Jefferies analyst Biren Amin saw the data as suggestive of the differentiation between IDO agents.
Newlink has a related drug called indoximod that also blocks IDO signaling, which showed promise at AACR in combination with Keytruda.
Amgen’s oncolytic virus combo
Dozens of the abstracts released Wednesday concerned various combination approaches to existing immuno-oncology treatments, most involving chemotherapy or another immunotherapy agent.
Amgen, though, included updated results from its open-label Phase 2 study testing its oncolytic virus together with Bristol-Myers Squibb’s Yervoy (ipilimumab). The study is the first randomized trial to evaluate pairing a oncolytic virus with a checkpoint inhibitor.
Results from 198 patients with late-stage melanoma showed treatment with the combo resulted in a 38.8% overall response rate, compared to 18% for those treated with Yervoy alone. Overall survival remains immature at this point but a median progression-free survival of 8.2 for the combo was recorded, versus 6.4 for Yervoy.
Safety data showed higher rates of adverse events for the combo, but none were unexpected.
Piper Jaffray analyst Joshua Schimmer views the data as a positive sign for other oncolytic therapies in development.
APHINITY details and early bispecifc results
A key part of Roche’s plans to defend its blockbuster HER2 breast cancer franchise rest on the success of its successor drug Perjeta (pertuzumab).
In early March, Roche announced Perjeta met its primary endpoint in the closely watched APHINITY study, improving invasive disease-free survival for people with HER2-positive early breast cancer when paired with Herceptin (trastuzumab) and chemo.
Full results from the study will be presented in a late-breaking abstract revealed at the ASCO meeting, and will likely receive much attention as the results could change the standard of care.
Roche also will present early results from its first T-cell bispecific antibody in CEA-positive cancers such as metastatic colorectal cancer. Phase 1a and 1b studies are testing the antibody, which targets CEA on tumor cells and CD3 on T-cells, both as a monotherapy and in combination with Tecentriq.