#AACR20 roundup: Tecentriq/Xtandi combo fails to show OS benefit, halting Roche's PD-L1 push into prostate cancer
For the first time in its 100-year-plus history, the American Association for Cancer Research is hosting its annual meeting completely online. Here’s a glance at some of the abstracts — which dropped early Monday — making the rounds:
Roche conceded that Tecentriq failed to help prostate cancer patients live longer when added to Xtandi, Pfizer and Astellas’ mainstay androgen receptor antagonist. The Phase III study dubbed IMbassador enrolled 759 patients with metastatic castration-resistant prostate cancer who had been treated with one prior line of chemotherapy and had progressed after taking androgen synthesis inhibitors.
On the primary endpoint of overall survival, no difference was observed between the Tecentriq/Xtandi and Xtandi groups. In fact, the median OS for the combo group was slightly shorter at 15.2 months compared to 16.6 months on the monotherapy arm.
“Subgroup analyses were consistent with the primary endpoint,” the investigators added in an abstract.
Researchers had hypothesized that Xtandi may enhance IFNɣ signalling and sensitive tumor cells to an immune attack. Mid-stage data from Merck have fueled that hope, but with the exception of a biomarker-based OK for Keytruda that potentially included prostate cancer, no PD-(L)1 drugs have been approved for the indication.
Roche is sponsoring a small, open-label study to evaluate using Tecentriq in the neoadjuvant setting. Merck, the leader in the checkpoint field, has a trio of Phase III trials underway, pairing Keytruda with Xtandi, Lynparza as well as chemo.
A Chinese biotech raises early hope for next-gen CAR-T
Will the next breakthrough in CAR-T be made in China? Gracell Bio is building its case for it.
The Shanghai-based biotech is reporting results from the first five adult patients treated with its allogeneic CAR-T for relapsed/refractory T-cell acute lymphoblastic leukemia. In a nutshell:
4 pts achieved MRD negative complete responses (MRD- CR) at D28 evaluation: 3 of them remained MRD- at follow-up re-evaluations (D118, 61, 161, respectively, and none was bridged to HSCT); 1 just achieved MRD- CR at D28 and follow-up results will be updated at the meeting. 1 pt achieved MRD+ CR at D14 but had relapsed disease at D29.
For the patients with a response, investigators documented peak expansions of the genetically engineered T cells between the first and second weeks after infusion of GC027.
Gracell attracted a well-heeled syndicate — featuring 6 Dimensions, Temasek and Lilly Asia Ventures — on the promise to overcome multiple constraints of traditional CAR-T: shrinking the manufacturing process from two weeks to one day, lowering the cost, as well as tweaking genes to avoid strong immune reactions.
But they weren’t exactly able to avoid the safety pitfalls that plagued the earlier products. Four patients experienced grade 3 cytokine release syndrome and the other one had grade 4 CRS along with elevated levels of IL6, IFNγ and TNFα — though all were resolved after treatment and supportive care.
After being knocked by a rejection from the FDA earlier this year, Merck has recently refiled a 6-week dosing schedule for Keytruda. At AACR, the pharma giant unveiled the clinical results behind the application.
The major takeaway from cohort B of KEYNOTE-555, the company said, is that administering 400 mg of Keytruda every six weeks yields comparable efficacy and safety as 200 mg every three weeks. At the interim analysis, overall response rate was 38.6% — a data point that adds to previous pharmacokinetic numbers.
Merck has already secured approval in Europe for the less frequent regimen, Q6W, which it said would offer greater flexibility for patients. It didn’t disclose details from the FDA’s complete response letter.