ESMO directly hit the melanoma innovation therapy has gains and losses, and the oncolytic virus is the perfect assist

preface

The 2022 Annual Meeting of the European Society of Oncology (ESMO) will be held

Oncolytic virus T-VEC

Patients with stage III.

Patients with resectable stage III.

As of 30 May 2022, the median follow-up period for all 150 patients was 63.

The final results of the largest randomized trial of neoadjuvant therapy in patients with resectable STAGE IIIB-IVM1a melanoma showed lasting improvement

Biased IL-2 pathway agonist

Bempegaldesleukin (BEMPEG) is a biased IL-2 signaling pathway agonist designed to stimulate a patient's own immune system to fight cancer
.

BEMPEG in combination with immune checkpoint inhibitors is expected to further improve efficacy
.

BEMPEG combined with the PD-1 inhibitor navuliyumab (NIVO) in patients with advanced melanoma showed clinical activity and controllable safety
in the Phase 1/2 PIVOT-02 study.

Based on this, the Phase 3, randomized, open-label PIVOT IO 001 study (NCT03635983) evaluated the efficacy and safety
of BEMPEG + navuliyuzumab versus navulilizumab in advanced melanoma.

The study included patients with previously untreated, unresectable or metastatic melanoma who were randomly assigned 1:1 to receive BEMPEG 0.
006 mg/kg IV + NIVO360 mg IV Q3W or NIVO 360 mg IV Q3W, stratified
by PD-L1 tumor cell expression, BRAF mutation status, and AJCCcv8M stage.

The primary endpoints were objective response rate (ORR), progression-free survival (PFS), and OS, all assessed
by blinded independent central review based on RECIST v1.
1.

Overall study significance levels were α 0.
05, ORR 0.
001, PFS 0.
03, and OS 0.
019
.

Hypothesis tests are both-sided
.

783 patients were randomly assigned to BEMPEG+NIVO (n=391) or NIVO (n=392); Baseline features remain balanced
across groups.

The median ORR follow-up was 19.
3 months and the median PFS follow-up was 11.
6 months
.

The results show:

• The ORR in the BEMPEG+NIVO group was 27.
  7%, while the NIVO monodrug group was 36.
  0% (bilateral P=0.
  0311).
  
  
  

• The disease control rate (DCR) was 56.
  1% in the BEMPEG+NIVO group and 58.
  5%
  in the NIVO monodrug group.
  
  

• The median PFS in the BEMPEG+NIVO group was 4.
  17 months (95% CI, 3.
  52-5.
  55), and the NIVO monodrug group was 4.
  99 months (4.
  14-7.
  82); HR 1.
  09; 97% CI, 0.
  88-1.
  35; P=0.
  3988
  。
  

• The median OS in the BEMPEG+NIVO group was 29.
  67 months (95% CI, 22.
  14-not reaching [NR]), and the NIVO monodrug group was 28.
  88 months (21.
  32-NR); HR=0.
  94; 99.
  93% CI, 0.
  59-1.
  48; and P=0.
  6361
  .
  
  

Swipe to see more

In terms of safety, the incidence of grade 3-4 drug-related adverse events (AE) and severe AE was higher
in the BEMPEG+NIVO monotherapy group compared with the NIVO monotherapy group.

The AE of particular concern is ischemic cerebrovascular events, with incidences of 2.
6% and 0.
8%
in the BEMPEG+NIVO group and NIVO monotherapy group, respectively.

There were 3 bemPEG+NIVO treatment-related deaths in the BEMPEG+NIVO group and 1 case
in the NIVO monotherapy group.

The study showed that in patients with advanced melanoma, BEMPEG+NIVO compared to NIVO showed no clinical efficacy
.

The primary endpoints ORR, PFS, and OS did not meet the pre-set statistical significance boundaries
.

Increased
toxicity of joint programmes.

Ongoing biomarker analysis may help further interpret the findings
.

References:

1.
R.
Dummer,et al.
Final 5-year results of the phase II, multicenter, randomized,open-label trial of talimogene laherparepvec (T-VEC) neoadjuvant treatment (Tx) plus surgery vs immediate surgery in patients ( pts) with resectable stage IIIB-IVM1a melanoma (MEL).
2022 ESMO.
Abstract LBA39.

2.
A.
Diab,et al.
PIVOT IO 001: First disclosure of efficacy and safety of bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) vs NIVO monotherapy in advanced melanoma (MEL).
2022 ESMO.
Abstract 785O.

Editing/Typography: Jiang Zhou

Execution: Small garden