POLARIX Trial – Efficacy Results

POLARIX PFS Results

POLIVY® + R-CHP: Superior PFS vs R-CHOP in the ITT Population^1,2

†No statistical hypothesis testing was performed for 2 year PFS data. No formal inferences may be drawn from these landmark analyses.

Exploratory analysis showed clear benefit of POLIVY® + R-CHP vs R-CHOP in several patient subgroups, including²: 

• Patients with an IPI score of 3-5 (PFS HR, 0.7;  2-year PFS difference, 10.1%) 
• Patients with activated B-cell-like (ABC) subtype of DLBCL (PFS HR, 0.4; 2-year PFS difference, 25.1%)
• Patients 60 years of age or older (PFS HR, 0.6; 2-year PFS difference, 12%)
• Patients without bulky disease (PFS HR, 0.7;  2-year PFS difference, 8.4%)

PFS – a clinically meaningful endpoint in DLBCL

• Phase 3 trials in 1L DLBCL have been commonly designed with PFS as the primary efficacy endpoint^3,4
  • In the POLARIX trial, PFS was defined as the time from randomization until the first occurrence of disease progression/relapse or death from any cause, whichever occurs earlier²
• In oncology, PFS is a common disease-related primary endpoint⁵
  • It can be assessed earlier than OS with fewer patients and is not confounded by subsequent therapies
  • PFS can represent direct clinical benefit^‡
• PFS is recognized by the US FDA as an important endpoint for drug approval in oncology⁵
  • PFS can be used as an endpoint to support accelerated or traditional approval^‡
• PFS assessment may be subject to limitations⁵
  • Definition of PFS may vary among studies and it may be subject to assessment bias and not always correlate with survival

^‡Based on specific disease, context of use, magnitude of the effect, the disease setting, location of metastatic sites, available therapy, the risk-benefit relationship, and the clinical consequences of delaying or preventing progression in key disease sites (e.g., delay of new lesions in the brain or spine) or delaying administration of more toxic therapies.

Select Secondary Endpoints

Superior EFS vs R-CHOP^1,2,§

• HR [95% CI]: 0.75 [0.58, 0.96]
• p-value^‖: 0.0244

^§Modified EFS is defined as the time from randomization to the earliest occurrence of disease progression or relapse, death, an efficacy finding that led to non-protocol specified lymphoma treatment, or biopsy positive for residual disease.
^‖Stratified log-rank test, with a two-sided significance boundary of 0.05. The hierarchical testing order was PFS, modified EFS, and then CR rate and overall survival.

Objective response at EOT in patients receiving POLIVY + R-CHP vs R-CHOP^1,¶

• Difference in CR rate, % [95% CI]: 3.9 [-1.9, 9.7]
• p-value^#: 0.1557

^¶By blinded independent central review, per 2014 Lugano response criteria.
^#Cochran-Mantel-Haenszel chi-squared test, with a two-sided significance boundary of 0.01.

Overall Survival data¹

• With an estimated median follow-up of 3.3 years, the prespecified final analysis of OS showed no statistically significant difference, with a HR of 0.94 [95% CI: 0.67, 1.33]
• In a descriptive analysis, the OS HR in patients with DLBCL, NOS was 1.02 [95% CI 0.70, 1.49], and in patients with HGBL it was 0.42 [95% CI: 0.15, 1.19]
  • No formal inferences may be drawn from this analysis

NE = Not Estimable; US = United States.

References: 

1. POLIVY, Israeli MoH approved prescribing information, Aug 2022.
2. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351​-363.
   
3. Iacoboni G, Zucca E, Ghielmini M, Stathis A. Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review. Ann Oncol. 2018;29(5):1120​-1129. doi:10.1093/annonc/mdy113
   
4. Poletto S, Novo M, Paruzza L, et al. Treatment strategies for patients with diffuse large B-cell lymphoma. Cancer Treat Rev. 2022;110:102443
   
5. Clinical trial endpoints for the approval of cancer drugs and biologics: guidance for industry. US Food and Drug Administration. December 2018. Accessed February 23, 2024. https://www.fda.gov/media/71195/download
   

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