Table 1 Characteristics of 17 patients who underwent dual matched targeted agent and immune checkpoint inhibitor simultaneously
From: Gene- and immune-targeted therapy combinations using dual-matched biomarkers for patient selection
ID (age/sex) | Cancer type | ECOG-PS | Number of lines of therapy | Dual-matched treatment | Rationale for ICI | Rationale for targeted therapy | Best response | PFS (Mos) | OS (Mos) | Comment |
|---|---|---|---|---|---|---|---|---|---|---|
1 (67/F) | Gynecologic (endometrial cancer) | 0 | 4 | Nivolumab Vismodegib | Nivolumab for TMB 12 Muts/Mb, MSI-high, ARID1A G95fs*10 | Vismodegib (hedgehog inhibitor) for PTCH1 S1203fs*52 | SD | 8.3 | 37.7+ | TMB 12 (Muts/Mb), MSI-high |
2 (40/M) | Glioblastoma | 3 | 1 | Nivolumab Cabozantinib | Nivolumab for PD-L1 positive (IC 5% by SP142) and PD-L1/L2 amplification | Cabozantinib (multi-kinase inhibitor including for MET, KIT, KDR and PDGFRA) for MET, KIT, KDR and PDGFRA amplifications | SD | 6.1 | 15.1 | TMB 2 (Muts/Mb) |
3 (60/M) | Gastro-esophageal | 1 | 2 | Nivolumab Lenvatinib Palbociclib | Nivolumab for PD-L1 positive (TC 10% IC 1% by SP142), ARID1A R1276* | Palbociclib (CDK4/6 inhibitor) for CCND1 and CDK6 amplifications Lenvatinib (multikinase inhibitor including for FGFR axis) for FGF3, FGF4, and FGF19 amplifications | PD | 0.9 | 2.6+ | TMB 8 (Muts/Mb) |
4 (84/F) | Peripheral T cell lymphoma | 0 | 2 | Trametinib Nivolumab | Nivolumab for PD-L1 positive (TC 1% by SP142) | Trametinib (MEK inhibitor) for NRAS Q61R | SD | 6.1 | 6.7 | TMB 6 (Muts/Mb) |
5 (54/M) | Gastro-esophageal | 1 | 1 | Nivolumab Lenvatinib Palbociclib | Nivolumab for PD-L1 positive (Tumor cell 1%, immune cell 1% by SP142 antibody) | Palbociclib (CDK4/6 inhibitor) for CDKN2A/B loss and CCND1 and CDK6 amplifications (all of which elevate CKD4.6 Lenvatinib for FGF3, FGF4, and FGF19 amplifications | PD | 2.6 | 2.6 | TMB 7 (Muts/Mb) |
6 (68/F) | Gynecologic (high grade serous adenocarcinoma of ovary) | 0 | 1 | Trametinib Nivolumab | Nivolumab for PD-L1 positive (IC 5% by SP142) | Trametinib (MEK inhibitor) for NF1 R440* | PR | 33.0 | 43.6 | TMB and MSI not available |
7 (86/M) | Bladder/Ureter | 1 | 2 | Atezolizumab Trastuzumab | Atezolizumab for PD-L1 positive (IC 5% by SP142) | Trastuzumab (HER2 inhibitor) for ERBB2 amplification | PD | 2.9 | 5.1+ | TMB 7 (Muts/Mb) |
8 (72/F) | Gastrointestinal stromal tumor | 1 | 4 | Pembrolizumab Lenvatinib | Pembrolizumab for ARID1A truncation exon 18 | Lenvatinib (multi-kinase inhibitor including for KIT) for KIT K558_E562del, N822K, V654A | SD | 12.9+ | 12.9+ | TMB 7 (Muts/Mb) |
9 (80/M) | Bladder/Ureter | 0 | 2 | Pembrolizumab Trastuzumab | Pembrolizumab for TMB 18 muts/Mb | Trastuzumab (HER2/ERBB2 antibody) for ERBB2 amplification | PD | 4.7 | 9.7 | TMB 18 (Muts/Mb) |
10 (51/F) | Gastro-esophageal | 1 | 4 | Pembrolizumab Ibrutinib | Pembrolizumab for ARID1A Q1519fs*13 and PD-L1 positive (CPS ≥ 50 by 22C3) | PR | 59.7 | 62.1+ | TMB and MSI not available | |
11 (67/M) | Gastro-esophageal | 1 | 1 | Nivolumab Bevacizumab Palbociclib | Nivolumab for PD-L1 positive (TC 5% by SP142) | Palbociclib (CDK4/6 inhibitor) for CCND3 amplification Bevacizumab (VEGF antibody) for VEGFA amplification | CR | 7.7 | 8.0 | TMB 5 (Muts/Mb) |
12 (20/F) | Cutaneous T cell lymphoma | 2 | 5 | Brentuximab Nivolumab | Nivolumab for PD-L1 positive (TC > 25%, IC > 25% by SP142) | Brentuximab (CD30 antibody) for CD30 positive by IHC | PD | 2.2 | 2.2 | TMB 7 (Muts/Mb) |
13 (69/F) | Bladder/Ureter | 1 | 4 | Pembrolizumab Trastuzumab | Pembrolizumab for TMB 14 muts/Mb | Trastuzumab (HER2/ERBB2 antibody) for ERBB2 S310F | SD | 6.3 | 15.7 | TMB 14 (Muts/Mb) |
14 (61/F) | Gynecologic (vulvar cancer) | 1 | 2 | Nivolumab Palbociclib Everolimus | Nivolumab for PD-L1 positive (IC 5% by SP142) | Everolimus (mTor inhibitor) for PIK3CA E545K Palbociclib (CDK4/6 inhibitor) for multiple alterations in CDKN2A (which elevate CDK4/6) | PD | 2.1 | 2.1 | TMB 8 (Muts/Mb) |
15 (69/F) | Malignant mixed Müllerian tumor | 1 | 3 | Nivolumab Trametinib Olaparib | Nivolumab for MSI-high, TMB 36 Muts/Mb, ARID1A P2005fs*10 | Trametinib (MEK inhibitor) for KRAS G12A Olaparib (PARP inhibitor) for BRCA2 T3033fs*29 | PD | 3.6 | 3.7 | TMB 36 (Muts/Mb), MSI-high |
16 (72/M) | Diffuse large B cell lymphoma | 2 | 2 | Pembrolizumab Venetoclax | Pembrolizumab for PD-L1 positive (TPS 60% by 22C3), TMB 14 Muts/Mb | Venetoclax (BCL-2 inhibitor) for IGH-BCL2 rearrangement | PD | 1.0 | 2.4 | TMB 14 (Muts/Mb) |
17 (37/M) | B cell lymphoma, unclassifiable | 0 | 2 | Brentuximab Pembrolizumab | Pembrolizumab for PD-L1 positive (TC 50%, IC 10% by SP142), TMB 16 Muts/Mb, ARID1A G149fs*77 | Brentuximab (CD30 antibody) for CD30 positive by IHC | PR | 23.4+ | 23.4+ | TMB 16 (Muts/Mb) |
