Oncology Pulse Masthead

September 2023

Overcoming PD-(L)1 Resistance

  • Overcoming checkpoint inhibitor (CPI) resistance has been a major area of investigation since the first PD-1 inhibitor was approved in 2014
  • Other than melanoma, PD-(L)1 re-challenge approaches have failed to show substantial benefit in randomized trials
  • Segmenting patients by resistance type may be a strategy for success, but only one of the pending Ph3 rechallenge trials in NSCLC is using this to select patients
  • Importantly, for any drug targeting the post-CPI setting, control arms of these failed trials hint that efficacy may be higher in CPI-pretreated patients

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1L checkpoint inhibitor approvals have improved efficacy for many solid tumors and also widened the gap between 1L and 2L SoC

Despite some promising early results, Phase 3 trials investigating PD-(L)1 re-challenge have only succeeded in melanoma

Data from NSCLC trials suggests efficacy may be limited to patients with acquired, rather than primary, CPI resistance

Median Overall Survival (mOS) by Type of Resistance

In addition, control arms from these trials suggest that CPI may impact the efficacy of subsequent therapies, particularly in RCC

Are pending rechallenge Ph3 trials in NSCLC likely to produce different results?

Optimism is higher for SWOG's trial that selects for patients with prior PD-(L)1 benefit

Pending Pivotal PD-(L)1 Retreatment Trials – NSCLC

Since our last Pulse, 6 new oncology agents have been approved (including 4 bispecifics for heme indications)

2023 New Oncology Agents



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