Table 1.
Clinical trials of ICIs plus targeted agents targeting BRAF/MEK, CDK, or ErbB.
| Cancer Type | Targeted Agents | Combination Agents | Phase | Control | Primary Endpoint | NCT Number |
|---|---|---|---|---|---|---|
| BRAF/MEK Inhibitors | ||||||
| Melanoma * | Cobimetinib + Vemurafenib | Atezolizumab | III | Cobimetinib + Vemurafenib + | PFS (vs. control): 15.1 vs. 10.6 months, HR = 0.78 | NCT02908672 |
| placebo | ||||||
| Melanoma | Trametinib + Dabrafenib | Ipilimumab + Nivolumab | III | Arm A: N/I + D/T | 2-year OS rate (Arm A vs. Arm B): 72% vs. 52% | NCT02224781 |
| Arm B: D/T + N/I | ||||||
| CDK Inhibitors | ||||||
| Breast Cancer | Palbociclib | Pembrolizumab + Letrozole | I/II | - | ORR: 56% | NCT02778685 |
| EGFR Inhibitors | ||||||
| HNSCC | Cetuximab | Pembrolizumab | II | - | ORR: 45% (95% CI 28–62) | NCT03082534 |
| CRC | Panitumumab | Ipilimumab + Nivolumab | II | - | ORR: 35% (95% CI 21–48) | NCT03442569 |
| CRC | Cetuximab | Pembrolizumab | Ib/II | - | A manageable safety profile | NCT02713373 |
| HER2 | ||||||
| HNSCC | Afatinib | Pembrolizumab | II | - | High PD-L1 expression (TPS ≥ 50 ORR: 71%, CPS ≥ 20 ORR: 63%); | NCT03695510 |
| EGFR amplification (ORR: 100%); | ||||||
| MTAP loss or mutation (ORR: 0%) | ||||||
| Oesophageal, G/GEJ Cancer | Trastuzumab | Pembrolizumab | II | - | 6-months PFSR: 70% (95% CI 54–83) | NCT02954536 |
| Breast Cancer | Trastuzumab | Pembrolizumab | Ib/II | - | ORR: 15% (90% CI 7–29) | NCT02129556 |
*: Approved by FDA. Source: http://www.clinicaltrials.gov (accessed on 29 July 2022). CRC, colorectal cancer; CDK, cycle-dependent kinase; CI, confidence interval; CPS, combined positive score; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; MEK, mitogen-activated protein kinase; MTAP, methylthioadenosine phosphorylase; ORR, overall response rate; PFS, progression-free survival; PFSR, progression-free survival rate; TPS, tumor proportion score.