Christopher R. Flowers, MD, MS
Professor of Hematology
and Medical Oncology
School of Medicine
The ongoing POLARIX clinical trial (NCT03274492) is investigating the novel investigational antibody–drug conjugate polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as a first-line therapy for patients with intermediate- or highrisk diffuse large B-cell lymphoma (DLBCL).1 The trial is currently open to enrollment in the United States and multiple global sites, with an estimated primary completion date of December 2019.
In a recent edition of OncLive©, Christopher R. Flowers, MD, MS, a member of the POLARIX: GO39942 Steering Committee and principal investigator of the Emory University School of Medicine study site, shared insights about the trial’s goals and design.2 Following is the complete interview with Dr Flowers, with expanded commentary.
OncLive: What type of patients are included POLARIX trial and what are some key exclusion criteria?
: Patients diagnosed with CD20-positive diffuse DLBCL of any subtype with an Eastern Cooperative Oncology Group performance status of 0 to 2, cardiac ejection fraction of at least 50%, and intermediate- or high-risk (International Prognostic Index [IPI] score of 2-5) are eligible for the study. Full description of the eligibility criteria can be found in the study.
How are participants randomized? Please describe the arms of the study.
Patients are randomized 1:1 into 2 groups: standard R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] given every 21 days for 6 cycles plus polatuzumab vedotin placebo, or R-CHP [rituximab, cyclophosphamide, doxorubicin, and prednisone] plus vincristine placebo and polatuzumab vedotin. Patients in both arms will also receive rituximab monotherapy in cycles 7 and 8.
Can you talk more about the study endpoints?
The investigators will assess the safety and efficacy of polatuzumab vedotin. The primary endpoint is investigator- assessed progression-free survival (PFS). Other endpoints include the rate of PET-negative complete response (CR) at the end of treatment, patient-reported outcomes, and potential biomarkers to predict improved outcomes and as a means for devising new therapeutic approaches in the future.
What prompted usage of polatuzumab vedotin in combination with R-CHP and R-CHOP?
Polatuzumab vedotin has been demonstrated to have encouraging efficacy when studied as monotherapy and in combination with anti-CD20 antibodies in the treatment of relapsed and refractory DLBCL, both by Palanca-Wessels and colleagues and Morschhauser and colleagues. Also, a doseescalation trial was conducted that revealed acceptable safety of polatuzumab in combination with R-CHP, and it established the dosing regimen for phase II trials [polatuzumab 1.8 mg/kg in combination with R-CHP].
What is the mechanism of action of polatuzumab vedotin?
Polatuzumab vedotin is a CD79b-specific antibody conjugated to a microtubule disrupting agent, monomethyl auristatin E, with a stable linker. CD79b is a component of a B-cell receptor restricted to mature B cells, except plasma cells, that is expressed by many B-cell hematologic malignancies. Polatuzumab vedotin is the first CD79b-directed antibody drug conjugated to a potent cytotoxin that is selectively delivered to tumor cells. This combination delivers highly potent cytotoxins directly to tumor cells, which then absorb the cytotoxin.
How does polatuzumab vedotin interact with R-CHP?
The standard of therapy for DLBCL is R-CHOP. RCHOP includes vincristine, unlike the studied arm which included polatuzumab vedotin with R-CHP in place of vincristine. Vincristine is a cytotoxic agent, and polatuzumab also works by delivering cytotoxin to tumor cells, but more selectively.
How are the drugs administered to patients? At what doses and schedules?
Patients in the R-CHOP plus polatuzumab vedotin placebo group will receive placebo for polatuzumab vedotin, rituximab 375 mg/m2
IV, cyclophosphamide 750 mg/m2
IV, doxorubicin 50 mg/m2
IV, and vincristine 1.4 mg/m2
IV (maximum 2 mg/dose) on day 1, and prednisone 100 mg/day orally on days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m2
IV will be administered as monotherapy in cycles 7 and 8.