Roche’s blood cancer portfolio is booming with new life thanks to the antibody-drug conjugate Polivy and bispecifics. Now, the company is offering a look at early-phase data for two combinations of those drugs that support two phase 3 trials in diffuse large B-cell lymphoma (DLBCL).
Roche kicked off the phase 3 SKYGLO trial in September, which adds its freshly FDA-approved CD20xCD3 bispecific drug Columvi on top of the Polivy-R-CHP regimen in previously untreated DLBCL. Now, data from the phase 1b NP40126 trial showed that Columvi plus Polivy-R-CHP helped 91.7% of 24 first-line patients achieve a complete response at the end of treatment with no disease progression after a median follow-up of 12 months.
That kind of progression-free survival data is “potentially best-in-class,” Charlie Fuchs, M.D., head of oncology and hematology global product development at Roche’s Genentech unit, said in an interview with Fierce Pharma.
The phase 1b readout also included 56 patients who received Columvi on top of the traditional R-CHOP regimen. There, the best complete response rate reached 83.9%; and the 12-month progression-free survival rate was estimated at 80.1%, compared with 91.5% for the Columvi-Polivy-R-CHP combo.
The Polivy paring with R-CHP received its frontline DLBCL nod from the FDA in April after showing it reduced the risk of progression or death by 27% compared with R-CHOP. Based on recent trends in uptake, Roche has increased its estimate for the Polivy regimen to now expect it to take up about 65% of the frontline DLBCL market.
The fact that now Columvi-Polivy-R-CHP is showing superior efficacy over Columvi-R-CHOP in phase 1b is giving Roche confidence in the SKYGLO trial compared with competitors, Fuchs said. Notably, AbbVie is also testing its Genmab-partnered rival CD20xCD3 bispecific antibody Epkinly on top of R-CHOP in newly diagnosed DLBCL in the phase 3 EPCORE DLBCL-2 trial.
Roche offers its CD20xCD3 T-cell engagers as fixed-duration therapies, whereas Epkinly is given indefinitely. Roche argues that allowing patients time free from treatment is important for their quality of life. But this design introduces the question of whether Roche’s therapy can sustain an anti-tumor effect over the long term. At the ASH meeting, the company offered longer follow-up data from the pivotal studies of Columvi and its other CD20xCD3 bispecific, Lunsumio, in heavily pretreated patients.
After a median follow-up of 32 months of the phase 2 NP30179 trial, 55% of Columvi patients who had previously achieved a complete response remained in remission after two years. At last year’s ASH, the trial showed 74% of complete responders were still in remission after a median follow-up of 18 months.
Among patients who had received prior CAR-T therapy, the complete response rate was similar with the overall population, and the median duration of complete responses among them was 22 months compared with 26.9 months for all patients.
Separately, for Lunsumio in previously treated follicular lymphoma, a three-year follow-up of the phase 2 GO29781 trial linked the drug to an estimated 72.7% rate for patients who had achieved a complete response to remain alive and without disease progression 30 months after their initial response. At last year’s ASH, investigators estimated that 79.5% of complete responders continued to have no sign of tumor after two years.
What’s more, among five patients who progressed after treatment and then received Lunsumio again, three recorded a complete response.
Between the two CD20 bispecifics, Roche is aiming the more powerful—and more toxic—Columvi at the more aggressive DLBCL, but it also has a phase 3 trial for Lunsumio in combination with Polivy in second-line DLBCL. That study, coded SUNMO, is expected to read out next year, and Roche also offered an update of early-phase data for that regimen.
In the phase 1b/2 GO40516 study, the Lunsumio-Polivy combo helped patients with pretreated large B-cell lymphoma live a median 11.4 months without disease progression. The median overall survival was 23.3 months. Cytokine release syndrome of grade 1 to 3 occurred in 18.4% of patients, with 3.1% at grade 3. Previously, investigators reported a 66% overall response rate and 49% complete responses from the trial.
The SUNMO trial requires that patients must have received at least one prior systemic therapy, and those who received only one prior treatment must be ineligible for stem cell transplants.
In DLBCL, Roche’s bispecifics need to compete with highly efficacious CAR-Ts. In the landmark Zuma-7 study, Gilead Sciences’ Yescarta reduced the risk of death by 27.4% compared with standard second-line therapy in patients with LBCL. But because the trial’s comparator was chemoimmunotherapy followed by stem cell transplant, only transplant-eligible patients were enrolled.
“The transplant-ineligible population, for any variety of reasons, either because of age or comorbid disease—that’s a sizable patient population that’s in need,” Fuchs said. If successful, Lunsumio and Polivy, as an off-the-shelf treatment, “will be an important therapeutic option in second line for those patients who aren’t necessarily ready for transplant but need durable, deliverable therapy.”