Alkermes is making a bit bet on its immuno-oncology program after swingeing cuts and R&D setbacks over the past year left its I-O program as one of its leading pipeline hopes.
Last October, the biopharma announced plans to slash around 160 employees, cut back its future hiring plans and reduce spending in an effort to save $150 million.
The move cost the company $15 million, and followed the FDA rejection of its depression drug ALKS 5461 last February. Back in April, it also lost Lisa von Moltke, M.D., who jumped ship to biotech Seres Therapeutics after acting as senior vice president and head of clinical development at Alkermes.
With ALKS 5461 out the window, Alkermes refocused its R&D business on its early-phase I-O program, known as ALKS 4230, as well as its schizophrenia drug, ALKS 3831.
Today, we got the first early look at what ALKS 4230, an engineered interleukin-2 (IL-2) variant immunotherapy, can do at the 2020 European Society for Medical Oncology (ESMO) Virtual Congress.
The data cover a series of targets as well as its use as a monotherapy and in combination with Merck’s blockbuster cancer drug Keytruda.
Breaking it down, the new clinical data come from its ongoing phase 1/2 trial, known as ARTISTRY-1, in patients with refractory solid tumors.
Top-line, Alkermes said the study “showed encouraging single-agent activity of ALKS 4230 in melanoma and durable responses in multiple tumor types in combination with pembrolizumab [Keytruda].”
On its own, ALKS 4230 (6 µg/kg/day) is being used in patients with refractory melanoma or refractory renal cell carcinoma. A total of 15 patients across both monotherapy cohorts were treated, with responses observed in melanoma.
In the melanoma cohort, of the five evaluable melanoma patients, one had a confirmed partial response (PR) and two had stable disease. Since the July 24 data cut, one additional melanoma patient achieved a PR, but is awaiting a confirmatory scan. As of Sept. 1, this additional patient had experienced a total tumor shrinkage of 39% and was continuing monotherapy treatment.
Hitting the two PRs among the first six evaluable patients also saw it reach the criteria needed to expand the test, and the cohort will now enroll up to 20 additional patients for a total of up to 41 patients.
Then there is its combination with checkpoint inhibitor Keytruda, which treated several solid tumors including refractory ovarian cancer. Of the 13 evaluable patients with progressive, refractory ovarian cancer, nine showed stable disease on their first scan.
Meanwhile, six of these nine patients received a second scan by the data cutoff date, and five had stable disease or better. All five of these ovarian cancer patients were heavily pretreated and platinum-resistant, and each experienced tumor burden reduction with the combination of ALKS 4230 and Keytruda.
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Of these five patients: One with platinum-resistant ovarian cancer achieved a complete response (CR) by week 45 of treatment, and a deepening of response was observed through week 81 of treatment. As of the data cut, this patient had a durable, confirmed CR and had remained on treatment for more than 18 months.
Two other patients with platinum-resistant ovarian cancer achieved PRs, one confirmed and one unconfirmed. As of the data cut, the patient with the confirmed PR demonstrated a deepening of response and had remained on treatment for more than five months.
Outside of ovarian cancer, additional PRs were hit across several other cohorts, including one patient with triple-negative breast cancer and two patients with esophageal cancer (one of which is awaiting confirmation). As of the data cut, these three patients had sustained PRs and continued on treatment.
“The fact that we saw monotherapy responses [with ALKS 4230] even in a pre-treated patient population, and these are some of the most refractory patients typically, and seeing responses in tough cancers like ovarian cancer is fairly remarkable and promising,” said Ulka Vaishampayan, M.D., lead investigator and professor of internal medicine in the division of hematology and oncology at the University of Michigan, speaking to Fierce Biotech ahead of the readout.
In terms of the combination cohorts, Keytruda is one of the biggest cancer drugs in the world with a growing list of indications in oncology; how can we know that Keytruda isn’t driving these responses, or that the combination of Keytruda and ALKS 4230 is working?
“The best way to show that is of course in a randomized study,” Vaishampayan said, but added that there were some clear indications Alkermes’ drug was working.
“There are other ways by which we can see: What we are testing against here, such as in ovarian cancer, we know checkpoint inhibitors [such as Keytruda] has not shown efficacy in those that have been pretreated.”
In fact, back in June during the virtual American Society of Clinical Oncology congress, Merck’s drug showed only modest clinical activity in patients with advanced recurrent ovarian cancer.
“So the fact that we are some activity in ARTISTRY-1 tells you that it must be enhancing something to show up that efficacy and response in that setting. The other thing is that there are other patients who have been pretreated with checkpoint inhibitors, failed, but then responded to the combination.”
On safety, Alkermes said that: “Based on the data available, ALKS 4230 in combination with [Keytruda] did not demonstrate any additive toxicity to that already established with [Keytruda] alone.”
There was, however, one death that came as a result of a pancreatic cancer in the combination cohort, which occurred after the data cutoff and was, according to Alkermes, “due to inanition (starvation) and assessed as related to both study drugs.”
Vaishampayan said that, overall, the drug appears to be “remarkably well tolerated,” despite the fact that IL-2 is known for having potentially high toxicities. She believed it was “impossible to separate out” the ultimate cause of the death.
“The patient was on both medications and the investigators, said there was some attribution possible from either of the medications.” She still believes it has a strong safety profile.