Table 3.
Clinical Trials of TLR9 Agonists in Combination Trials
| TLR9 Agonist | Study Phase | Histology | Combination Agent | ROA | Efficacy |
|---|---|---|---|---|---|
| PF-3512676 (CPG 7909)173 | II | Advanced metastatic melanoma | MART-1 (26–35, 27L), gp100 (209–217, 210M), and tyrosinase (368–376, 370D) vaccine with GM-CSF | SC 1.8mg every 2 weeks | ORR 9% (2/22) SD rate 36% (8/22) |
| PF-3512676 (CPG 7909)176 | II/III | Advanced metastatic melanoma | PF-3512676 ± DTIC 850mg/m2 | SC 10mg vs 40mg weekly | ORR: PF-3512676 10mg 2% PF-3512676 40mg 0% PF-3512676 40mg + DTIC 16% DTIC 8% |
| PF-3512676 (CPG 7909)177 | III | Advanced chemotherapy-naïve NSCLC | Carboplatin AUC6 with paclitaxel 200mg/m2 ± PF-3512676 | SC 0.2mg/kg every 2 weeks | ORR: Carboplatin/paclitaxel 23% Carboplatin/paclitaxel + PF-3512676 28% Median OS: Carboplatin/paclitaxel 9.8 months Carboplatin/paclitaxel + PF-3512676 10.0 months |
| PF-3512676 (CPG 7909)178 | II | Advanced chemotherapy-naïve NSCLC | Carboplatin AUC 6 or cisplatin 75mg/m2 with paclitaxel 175mg/m2 or docetaxel 75mg/m2 ± PF-3512676 |
SC 0.2mg/kg every 2 weeks | ORR: Chemotherapy 11% Chemotherapy + PF-3512676 19% Median OS: Chemotherapy 6.8 months Chemotherapy + PF-3512676 12.3 months |
| IMO-2055179 | IB | Advanced chemotherapy-refractory NSCLC | Erlotinib 150mg daily + bevacizumab 15mg/kg q3 + IMO-2055 | SC 0.08–0.48 mg/kg weekly | ORR 15% (5/33) |
| PF-3512676 (CPG 7909)180 | II | Advanced recurrent EGFR mutant NSCLC | Erlotinib 150mg daily ± PF-3512676 | SC 0.2mg/kg weekly | ORR: Erlotinib 5% (1/21) Erlotinib + PF-3512676 10% (2/22) Median PFS: Erlotinib 1.7 months Erlotinib + PF-3512676 1.6 months Median OS: Erlotinib 4.7 months Erlotinib + PF-3512676 6.4 months |
| PF-3512676 (CPG 7909)181 | I | Advanced chemotherapy-naïve NSCLC Japanese patients | Carboplatin AUC6 with paclitaxel 200mg/m2 and PF-3512676 | SC 0.1 vs 0.2mg/kg every 2 weeks | ORR 8% (1/12) SD rate 25% (3/12) |
| PF-3512676 (CPG 7909)182 | III | Advanced chemotherapy-naïve NSCLC | Cisplatin 75mg/m2 with gemcitabine 1250mg/m2 ± PF-3512676 | SC 0.2mg/kg weekly | ORR: Chemotherapy 31% Chemotherapy + PF-3512676 32% Median PFS: Chemotherapy 5.1 months Chemotherapy + PF-3512676 5.1 months Median OS: Chemotherapy 10.7 months Chemotherapy + PF-3512676 11.0 months |
| IMO-2055183 | IB | Advanced chemotherapy-refractory CRC | FOLFIRI/cetuximab with escalating doses of IMO-2055 | SC 0.16–0.48mg/kg weekly | ORR 14% (2/14) |
| PF-3512676 (CPG 7909)186 | I | Advanced melanoma and other solid tumors | Tremelimumab 6.0, 10.0, or 15.0 mg/kg every 12 weeks with escalating doses of PF-3512676 | SC 0.05–0.15mg/kg weekly | ORR 12.5% (2/16) |
| Lefitolimod (MGN1703)189 | II open-label | ES SCLC following response (CR/PR) to 1L platinum-based chemotherapy | Cycle 5 and 6 of platinum-based chemotherapy ± lefitolimod (MGN1703) | SC 60mg twice weekly | ORR: Chemotherapy 8% Chemotherapy + MGN1703 12% Median PFS: Chemotherapy 4.0 months Chemotherapy + MGN1703 3.2 months Median OS: Chemotherapy 9.7 months Chemotherapy + MGN1703 10.0 months |
| Lefitolimod (MGN1703)190 | II blinded, placebo-controlled | CRC following disease control (CR/PR/SD) to 1L platinum-based chemotherapy ± bevacizumab | Lefitolimod (MGN1703) or placebo | SC 60mg twice weekly | Median PFS: Placebo 2.6 months MGN1703 2.8 months Median OS: Placebo 15.1 months MGN1703 22.6 months |
| SD-101154 | Phase Ib | Advanced metastatic PD-1 refractory and PD-1 naïve melanoma | Pembrolizumab 200mg q3w with IT SD-101 | IT 1, 2, 4, 8mg weekly | ORR (PD-1 naïve) 100% (7/7) ORR (PD-1 refractory) 17% (2/12) |
| CMP-001167 | Phase Ib | Advanced metastatic PD-1 refractory melanoma | Pembrolizumab 200mg q3w with IT CMP-001 | IT 5 or 10mg weekly for 7 weeks then q3w | ORR (CMP-001 dose-escalation) 23% (10/44) ORR (1st expansion) 15% (10/69) ORR (2nd expansion) 26% (8/31) |
Abbreviations: AUC, area under curve; DTIC, dacarbazine; ES SCLC, extensive-stage small cell lung cancer; IT, intratumoral; PFS, progression-free survival; ORR, overall response rate; OS, overall survival; Q3W, every 3 weeks; SC, subcutaneous; SD, stable disease.