FDA Approves Tecentriq for ctDNA-Guided Bladder Cancer and Venclexta Plus Acalabrutinib for CLL

The U.S. Food and Drug Administration has approved two new cancer therapies from Genentech: Tecentriq (atezolizumab) as an adjuvant treatment for muscle-invasive bladder cancer guided by circulating tumor DNA testing, and Venclexta (venetoclax) plus acalabrutinib as a first-line fixed-duration regimen for chronic lymphocytic leukemia.

Tecentriq for ctDNA-Guided Bladder Cancer

The FDA approved Tecentriq and Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) as an adjuvant treatment for adult patients with muscle-invasive bladder cancer (MIBC) who have circulating tumor DNA molecular residual disease (ctDNA MRD) after cystectomy, as identified by Natera's Signatera CDx personalized MRD assay. This represents the first approval of a ctDNA-guided therapy.

The decision was based on positive results from the Phase III IMvigor011 study, which showed that Tecentriq reduced the risk of disease recurrence or death (DFS) by 36% and the risk of death (OS) by 41% in patients with detectable ctDNA MRD identified via serial testing within one year of cystectomy. The safety profile was generally consistent with previous studies of Tecentriq. IMvigor011 is the first prospective Phase III study to demonstrate that a ctDNA-guided approach to adjuvant therapy can significantly improve survival in MIBC.

Each year, over 150,000 people worldwide are diagnosed with MIBC and undergo bladder removal surgery. Even after surgery, nearly half of these patients see their cancer return. The IMvigor011 study utilized the Natera Signatera personalized ctDNA assay to identify molecular evidence of cancer in the blood before it becomes visible with standard imaging. The surveillance phase included 761 people who underwent serial ctDNA testing for up to a year after surgery. Of these, 250 people who tested positive for ctDNA joined the treatment phase, where they received either Tecentriq or placebo. The Signatera CDx test received simultaneous authorization by the FDA for use as a companion diagnostic to Tecentriq.

Venclexta Plus Acalabrutinib for CLL

The FDA also approved the combination regimen of Venclexta (venetoclax) plus acalabrutinib (Calquence, AstraZeneca) for the treatment of previously untreated adults with chronic lymphocytic leukemia (CLL), including small lymphocytic lymphoma. The regimen is the first and only all-oral, fixed-duration regimen designed to provide patients with the potential to experience time off treatment.

The approval was based on results from the Phase III AMPLIFY study, which demonstrated that Venclexta plus acalabrutinib was superior to chemoimmunotherapy. The combination regimen reduced the risk of disease progression or death by 35% versus chemoimmunotherapy (HR 0.65; 95% CI: 0.49-0.87; p=0.0038). At a median follow-up of 42.6 months, median progression-free survival was not reached for the combination regimen (95% CI: 51.1 months, not reached) versus 47.6 months (95% CI: 43.3 months, not reached) for chemoimmunotherapy.

In AMPLIFY, previously untreated adults with CLL without del(17p) or TP53 mutation were randomized 1:1:1 to receive AV, AV plus obinutuzumab for a fixed duration, or investigator's choice of chemoimmunotherapy. Patients in the AV arms were treated for 14 28-day cycles. At a median follow-up of 41.0 months, there were 18 (6%) versus 42 (14%) deaths in the arms, respectively.

The safety profile of the combination was consistent with the known safety profile of each individual therapy alone. The most common adverse reactions (≥20%) were neutropenia, headache, diarrhea, musculoskeletal pain, and COVID-19. The most common serious adverse reactions (≥2%) were COVID-19 including COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%).

The recommended regimen consists of up to 14 28-day cycles of acalabrutinib and 12 cycles of venetoclax starting at cycle 3. The recommended acalabrutinib dose is 100 mg approximately every 12 hours until disease progression, unacceptable toxicity, or completion of 14 cycles. Venetoclax should be started at 20 mg according to the 5-week ramp-up dosing schedule, followed by 400 mg once daily until disease progression, unacceptable toxicity, or until the last day of cycle 14.

CLL is one of the most common forms of leukemia in adults. While outcomes have improved in recent years, patients often face long treatment durations and ongoing disease management challenges. An estimated 22,760 new cases of CLL are expected in the U.S. in 2026.