ASH 2024: Phase III Study of Glofitamab Plus Pola-R-CHP Ongoing in Patients with Previously Untreated CD20-Positive LBCL

Combination therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, known as R-CHOP, is a standard first-line treatment option for patients with diffuse large B-cell lymphoma (DLBCL). Durable remissions are observed in about 60% of patients who receive R-CHOP, and recent efforts have focused on new combinations that can help deepen remissions and extend progression-free survival.

Several advancements in DLBCL treatment have been made in recent years, including the approval of the Pola-R-CHP, an R-CHOP derivative that includes the addition of the antibody-drug conjugate polatuzumab vedotin. A novel CD20-directed bispecific antibody known as glofitamab has also been approved for use in relapsed/refractory DLBCL for patients who have received at least 2 other prior lines of therapy. In preliminary trials, use of glofitamab in combination with the Pola-R-CHP regimen has shown promise in the first-line treatment setting for DLBCL, including for those with high-risk disease.

To expand upon these results, Foundation SAB member Ranjana H. Advani, MD of Stanford Cancer Institute presented the design of a new phase III study, SKYGLO, which will evaluate the efficacy and safety of glofitamab plus Pola-R-CHP versus Pola-R-CHP alone in patients with previously untreated CD20-positive LBCL.

The SKYGLO study began enrollment in September 2023 and will include an anticipated 1130 adults (up to 80 years of age) from up to 260 centers from around the world. Participants will be randomized to receive either glofitamab plus Pola-R-CHP or Pola-R-CHP alone for 8 cycles of 21 days each. The primary endpoint of the study will be progression-free survival, defined as the time from randomization to the first occurrence of
disease progression, relapse, or death. Other endpoints will include safety, response rates, and overall survival. Survival rates will also be analyzed based on risk status to assess the efficacy in patients with high-risk disease.

This study also included contributions from former Foundation SAB member Brad Kahl, MD of Washington University Medical School, and Foundation SAB member and grantee Alex Herrera, MD of City of Hope.