ASCO: AbbVie, J&J pad Imbruvica's CLL case with Venclexta fixed-duration combo data

Long-term data showed that at six and a half years, 61% of chronic lymphocytic leukemia patients on AbbVie and Johnson & Johnson's Imbruvica were still alive without disease progression. (AbbVie, Johnson & Johnson)

AbbVie and Johnson & Johnson’s Imbruvica is under increasing pressure from new in-class competitors, but the pair hopes a new combination and longer-term data could help consolidate its lead in chronic lymphocytic leukemia.

In previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), combining Imbruvica with AbbVie and Roche’s Venclexta eradicated cancer in 56% of patients after 12 cycles of treatment, new phase 2 data show.

The goal of the CAPTIVATE study was to show that a fixed duration of Imbruvica-Venclexta treatment could deliver a meaningful response, Craig Tendler, vice president of oncology clinical development and global medical affairs at J&J’s Janssen unit, said in an interview.

While continuous single-agent Imbruvica has established itself as a standard of care in front-line CLL, the hope is that the new 15-month regimen—including three months of lead-in therapy with solo Imbruvica—could offer patients some off time from treatment, he said.

“It’s all about flexibility and providing an additional option to fulfill the different needs of patients; some who are younger and would prefer this type of time-limited treatment,” Tendler said.

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About 70% of patients in the fixed-duration arm of the Captivate study showed undetectable levels of minimal residual disease (MRD)—a more stringent measure of leukemia cells in the body—in peripheral blood at some point during the median 27.9 months of follow-up.

And about 60% achieved that measure in bone marrow, again at some point during the follow-up period. Ninety-five percent of patients were still alive without disease progression after two years.

The results, to be presented at the American Society of Clinical Oncology (ASCO) virtual meeting next month, were similar for patients with del(17p) mutations, a high-risk factor.

In another cohort of the same study, AbbVie and J&J previously showed that 95% of patients who achieved undetectable MRD in both the blood and bone marrow upon completing the fixed-duration regimen remained disease-free one year after stopping treatment.

For the eight patients who progressed after stopping treatment, six responded to subsequent Imbruvica monotherapy, with the other two pending a response report, according to Tendler.

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“It’s a very important part of this treatment regimen to be able to show that you’re able to reinduce a remission if the patient has unfortunately progressed,” Tendler said. It gives the pairing early confidence that stopping treatment as the regimen intended doesn’t pose undue risk to patients, he added.

As the first-to-market BTK inhibitor, Imbruvica now faces increased competition from AstraZeneca’s Calquence and BeiGene’s Brukinsa, both of which have topped Imbruvica on a heart safety marker in their respective head-to-head CLL clinical trials.

Tendler pointed out that those head-to-head trials were in previously treated patients and had a relatively short follow-up time, suggesting incident rates of atrial fibrillation and flutter might change over the long term. Physicians have had years of experience with Imbruvica, and the drug boasts longer follow-up clinical trial data, he pointed out.

At ASCO, AbbVie and J&J also presented more follow-up data from the phase 3 RESONATE-2 trial, which earned Imbruvica its original FDA front-line CLL nod in 2016.

After a median 74.9 months and up to seven years of follow-up, Imbruvica registered an 84% reduction in the risk of progression or death over legacy chemotherapy chlorambucil. At six and a half years, 61% of patients on Imbruvica were still alive without disease progression, versus 9% for the chemo group.

For the Imbruvica-Venclexta fixed-duration cocktail, AbbVie and J&J have a phase 3 trial dubbed GLOW that’s pitting the regimen against a combo of chlorambucil and Roche’s anti-CD20 drug Gazyva in newly diagnosed CLL/SLL. The study will report progression-free survival data later this year, Tendler said.