Trillium is hunting giants with its anti-CD47 drug, but questions over a high-dose solo regimen still linger
CD47 player Trillium Therapeutics released a new slate of data for two of its experimental cancer drugs on Wednesday, updating previously released results from last winter’s ASH conference. But even though higher doses of the programs were administered since then, the overall response rates stayed roughly the same.
As of the new April 12 data cutoff for the lead TTI-622 program, 9 of 27 evaluable patients with relapsed or refractory lymphoma recorded an objective response, good for a 33% ORR. That rate fell slightly from the ASH data cutoff, where 6 of 17 evaluable patients saw responses, or 35%. One new complete response and two new partial responses were observed at the two highest doses since the ASH update, Trillium said.
The company is still waiting to collect data from three more patients at the high dose level as well, so final results of the study could change further.
In an interview with Endpoints News, CEO Jan Skvarka said he isn’t concerned about the difference. He pointed out that there’s no statistical difference between the 33% and 35% figures, asserting 33% remains a “very meaningful number.” Skvarka contextualized TTI-622’s response rate by comparing it with Merck’s Keytruda, saying that among its 19 indications it typically sees rates between 15% and 40%.
TTI-622 also put forth the highest rate among anti-CD47 monotherapy programs, Skvarka asserted, a key differentiating factor from other players in the field using combination therapies.
“It’s a little bit fuzzy with different indications and so on, but nevertheless it is the highest response rate observed in the field,” Skvarka told Endpoints.
During the company’s R&D day Wednesday, Trillium contrasted their monotherapy rates with some competitors in a presentation deck. There was the Gilead candidate magrolimab, acquired in the March 2020 buyout of Forty Seven, as well as an ALX Oncology program called ALX148. Trillium said its 33% ORR across all doses and tested lymphomas proved favorable to a magrolimab ORR of 10% in acute myeloid leukemia and myelodysplastic syndrome, data Trillium pulled from Forty Seven’s ASCO presentation in 2019.
Additionally, the ALX candidate registered no responses as of its own 2018 ASCO update in solid tumors. And Trillium further pointed out that TTI-622 response rates as a monotherapy in relapsed and refractory DLBCL (27%) stood up well to a magrolimab plus Rituxan combo (36%) and ALX148/Rituxan study (18% and 33% at two dosages) in the same field.
Skvarka readily conceded that no head-to-head data exist to directly compare these programs. But he offered that once Trillium begins testing TTI-622 in combination with chemotherapy, monoclonal antibodies and PD-1 inhibitors, the program is hoping to see even better responses than its 33% released Wednesday.
“The numbers you see from the monotherapy drug, these are our numbers, they’re not coming from some combination agent,” Skvarka said. “What you see are our response rates, but more importantly it’s the foundation of our next steps.”
With that strategy comes an aggressive clinical trials portfolio, which Trillium announced Wednesday will span seven different indications including three in solid tumors. The company plans to launch each of these studies over the next 12 months, looking to combine TTI-622 with other agents in p53 mutant AML patients, platinum-resistant ovarian cancer and DLBCL, among others.
The highest dose tested in the proof-of-concept study was 18 mg/kg, and the dose being advanced into the new trials is 8 mg/kg.
Trillium’s programs focus on the protein CD47, which tumors hijack in order to instruct the immune system’s first responder-like macrophages to not destroy them — colloquially known as the “don’t eat me” signal. Blocking CD47, researchers have reasoned, could theoretically get the immune cells to attack the cancer in the way they’re supposed to.
The space got a huge boost from Gilead’s acquisition of Forty Seven for nearly $5 billion. Founded by Stanford stem cell pioneer Irv Weissman, the subsidiary has focused the majority of its efforts on magrolimab and earned a breakthrough therapy designation for myelodysplastic syndrome last September.
In its most recent data update from last December, magrolimab saw progress in a Phase Ib trial for first-line AML. Among 43 evaluable patients treated with magrolimab plus azacitidine chemotherapy, 27 saw at least a partial response. That registered as a 63% ORR.