ASCO 2019 | Polatuzumab vedotin + obinutuzumab + lenalidomide for R/R FL

On Tuesday 4^th June an oral abstract session took place at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. During that session, Abstract 7505 was presented by Catherine Diefenbach, NYU Langome Health, New York, NY, USA, on a phase Ib/II clinical trial involving polatuzumab vedotin combination therapy.

Polatuzumab vedotin is a first-in-class antibody-drug conjugate that targets CD76b, a protein expressed in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Polatuzumab vedotin in combination with rituximab, and bendamustine was approved by the FDA on June 11, 2019 for the treatment of relapsed or refractory (R/R) DLBCL.²

This open-label, single-arm, phase Ib/II study assessed the safety and preliminary efficacy of polatuzumab vedotin in combination with obinutuzumab and lenalidomide (Pola-G-Len), in patients with R/R FL. The primary efficacy endpoint of the trial was complete response (CR) at the end of induction treatment, as assessed by an independent review committee (IRC) based on PET-CT scans. Here the speaker presented the results of the pre-planned interim analysis of the trial.

Study design

• N = 52 patients with R/R FL Grade 1–3a with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2
• Dosing:
  • Pola-G-Len induction treatment (six 28-day cycles):
    • Polatuzumab vedotin (Pola): 1.4mg/kg or 1.8mg/kg (dose escalation) intravenously (IV) on Day 1 of each cycle
    • Obinutuzumab (G): 1000mg IV on Day 1, 8, 15 of cycle 1 and on Day 1 of cycles 2–6
    • Lenalidomide (Len): 10mg, 15mg or 20mg (dose escalation) orally on Days 1–21 of each cycle
  • G-Len maintenance (28-day cycles): patients in CR, partial response (PR) or stable disease (SD) after Pola-G-Len induction received maintenance:
    • G: 1000mg on Day 1 every two months for 24 months
    • Len: 10mg on Days 1–21 monthly for 12 months
  • Median follow-up: 6 months
    

Table 1. Key baseline characteristics

Baseline characteristic

Efficacy population
(n= 18)

Safety population
(n= 52)

Median age (range)

58 (53–68)

62 (32–87)

ECOG PS 0–1

94%

98%

Ann Arbor stage III–IV

94%

88%

FL International Prognostic Index (FLIPI)≥ 3

44%

58%

Number of prior lines:

1

2

≥3

 

17%

22%

61%

 

21%

21%

58%

Median number of prior lines (range)

3 (1–5)

3 (1–7)

Refractory to last line

50%

50%

Key results

Pre-planned interim analysis data

Table 2. Key efficacy outcomes

Response at end of induction (n= 18), % (n)

Modified Lugano 2014 criteria by IRC

Objective response

89% (16)

CR

67% (12)

PR

22% (4)

SD

6% (1)

Disease progression (PD)

0 (0)

Missing/not evaluable/not available

6% (1)

• At a median follow-up of 16.6 months (range, 3.2–25.1):
  • Median progression-free survival (PFS): not reached
  • 12-month PFS rate: 90%
• To date:
  • Two out of 17 responders have experienced PD
  • The remaining patients have ongoing responses (longest one > 21 months)

Safety (n= 52 evaluable patients)

• Patients with ≥1 adverse event (AE): 100%
• Grade 5 AEs: n= 1 (2%)
• Grade 3–4 AEs: n= 39 (75%), with the most common hematological Grade 3–4 AEs being:
  • Neutropenia (46%)
  • Thrombocytopenia (17%)
  • Anemia (12%)
  • Febrile neutropenia (4%)
• Non-hematological Grade 3–4 AEs observed were:
  • Infections (12%)
  • Alanine aminotransferase increase (4%)
  • Increased lipase (4%)
  • Hypokalemia (4%)
  • Tumor lysis syndrome (4%)
• Serious AEs occurred in 40% of patients (n= 21)
• AEs leading to Len dose alteration or discontinuation: n= 43 (83%)

Conclusions

• Pola-G-Len led to a good objective response rate (89%) after induction and durable responses in R/R FL, with 90% of patients remaining progression-free one-year post treatment
• Pola-G-Len has a manageable toxicity profile consistent with the published profiles for each drug
• The primary analysis of the trial is expected in the near future