Next-Generation Checkpoint Targets

Immune checkpoints beyond PD-1: LAG-3, TIGIT and TGF-beta blockade added to an anti-PD-(L)1 backbone, and whether a second target improves response or only adds toxicity.

4 articles in this topic

• August 3, 2026Cancer DiscoveryNCI 18-C-0110 (NCT03554473)

  TGF-β Blockade Plus PD-L1 Inhibition Triggers Hyperprogression in Relapsed Small Cell Lung Cancer

  A single-center, investigator-initiated Phase Ib/II trial (NCI protocol 18-C-0110, NCT03554473) tested bintrafusp alfa — a bifunctional PD-L1/TGF-β fusion protein — alone or with chemotherapy in 37 patients with relapsed small cell lung cancer treated between 2019 and 2022.

• July 30, 2026JAMA OncologyI-SPY2 (NCT01042379)

  Dual PD-1/LAG-3 Blockade Nearly Doubles Complete Response in High-Risk Breast Cancer

  A Phase 2 arm of the adaptive I-SPY2 platform trial (78 patients treated 2020-2021, compared against 350 historical controls) tested adding cemiplimab (anti-PD-1) and fianlimab (anti-LAG-3) to neoadjuvant chemotherapy in high-risk, stage II-III, ERBB2 (HER2)-negative breast cancer.

• July 10, 2026Nature MedicineABTC 1501 (NCT02658981)

  Phase 1 Trial: Anti-LAG-3 Plus Anti-PD-1 Shows Acceptable Safety in Recurrent Glioblastoma

  Open-label, multicenter phase 1 trial (Adult Brain Tumor Consortium, ABTC 1501) of the anti-LAG-3 antibody relatlimab, alone or combined with the anti-PD-1 antibody nivolumab, in 46 patients with first-time recurrent glioblastoma (GBM)

• February 13, 2026Lancet OncologyKEYVIBE-010 (NCT05665595)

  KEYVIBE-010: Adding Vibostolimab to Pembrolizumab Does Not Improve Outcomes in Resected High-Risk Melanoma

  Randomised, double-blind, phase 3 study of 1,402 patients with surgically resected stage IIB–IV cutaneous melanoma across 205 global sites