Table 3.
Other combinations in clinical trials with immunomodulatory monoclonal antibodies.
| Trial identifier/study phase/status | Combination therapy | Patient condition | Sponsor | Official study title | Study design |
|---|---|---|---|---|---|
| NCT01740297 Phase I/II (completed, 2015) | • Ipilimumab (antagonist CTLA-4 mAb) • talimogene laherparepvec (oncolytic virus) | Metastatic melanoma (MM) | Amgen | Phase 1b/2, multicenter, open-label trial to evaluate the safety and efficacy of talimogene laherparepvec and ipilimumab compared to ipilimumab alone in subjects with unresected, stage IIIB-IV melanoma | • Experimental: Phase 1b and Phase 2 Arm 1. Talimogene laherparepvec plus ipilimumab. • Active Comparator: Phase 2 Arm 2. Ipilimumab |
| NCT02263508 Phase Ib/III (recruiting, 2014) | • Pembrolizumab (antagonist PD-1 mAb) • talimogene laherparepvec (oncolytic virus) | MM | Amgen | A Phase 1b/3, multicenter, trial of talimogene laherparepvec in combination with pembrolizumab (MK-3475) for treatment of unresectable stage IIIB to IVM1c melanoma (MASTERKEY-265/KEYNOTE-034) | • Experimental: Phase 3 Arm 1, talimogene laherparepvec and pembrolizumab (MK-3475). • Experimental: Phase 3 Arm 2: placebo and pembrolizumab (MK-3475) |
| NCT02272855 phase II (ongoing, not-recruiting, 2014) | • Ipilimumab (agonist CTLA-4 mAb) • HF10 (vaccinia virus) | MM | Takara Bio Inc | A Phase II study of combination treatment with HF10, a Replication-competent HSV-1 oncolytic virus, and ipilimumab in patients with Stage IIIB, Stage IIIC, or Stage IV unresectable or metastatic malignant melanoma | Patients will receive 1.107 TCID50/mL HF10 (four injections/once a week; two injections/once at 3 weeks) and ipilimumab 3 mg/kg IV/3 weeks/four total doses |
| NCT03003676 Phase I (recruiting, 2016) | • Pembrolizumab (antagonist PD-1 mAb) • ONCOS-102 (oncolytic virus) | MM | Targovax Oy | A pilot study of sequential ONCOS-102, an engineered oncolytic adenovirus expressing GMCSF, and pembrolizumab in patients with advanced or unresectable melanoma progressing after PD1 blockade | Patients will receive three doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, and 8) at 3 × 1011 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1–3 days prior to day 1. They will then receive pembrolizumab i.v., 2 mg/kg, on day 22 (week 3) and every 3 weeks thereafter until the end of treatment visit on day 169 (week 24) |
| NCT01986426 Phase I (recruiting, 2013) | • Ipilimumab (antagonist CTLA-4 mAb) • pembrolizumab (antagonist PD-1 mAb) • LTX-315 (lytic peptide) | Metastatic tumors including MM | Lytix Biopharma AS | A Phase I, open-label, multiarm, multicenter, multi-dose, dose escalation study of LTX-315 as monotherapy or in combination with either ipilimumab or pembrolizumab in patients with transdermally accessible tumors | • Arm A: LTX-315 monotherapy at single/sequential lesions. • Arm B: LTX-315 monotherapy at concurrent multiple lesions. • Arm C: LTX-315 plus ipilimumab in MM patients. • Arm D: LTX-315 plus pembrolizumab in triple-negative breast cancer patients |
| NCT02302339 Phase II (recruiting, 2016) | • Glembatumumab vedotin (gpNMB conjugate-drug mAb) • varlilumab (CD27 agonist mab) • nivolumab/pembrolizumab (antagonist PD-1 mAb) | MM | Celldex Therapeutics | A Phase 2 study of glembatumumab vedotin, an anti-gpNMB antibody–drug conjugate, as monotherapy or in combination with immunotherapies in patients with advanced melanoma | • Cohort A: glembatumumab vedotin IV on day 1/21 day cycle. • Cohort B: glembatumumab vedotin IV on day 1/21 day cycle. Varlilumab IV on day 1 of cycles 1, 2, 4, 6, 8 and 10. • Cohort C: glembatumumab vedotin IV on day 1/21 day cycle. Nivolumab/pembrolizumab administered according to institutional standard of care |
| NCT02076633 Phase II (completed, 2015) | • L19IL2 (HDAC4 mab conjugated with IL-2) • L19TNF (HDAC4 mab conjugated with TNF) | MM | Philogen S.p.A. | A Phase II study of intratumoral application of L19IL2/L19TNF in melanoma patients in clinical Stage III or Stage IV M1a with presence of injectable cutaneous and/or SC lesions | Patients will be treated with intratumoral injections of 10 Mio IU L19IL2 and 312 µg L19TNF once weekly for up to 4 weeks |
| NCT02315066 Phase I (recruiting, 2015) | • PF-04518600 (agonist OX40 mAb) • PF-05082566 (agonist 41BB mAb) | Metastatic tumors including MM | Pfizer | A Phase 1, open-label, dose escalation study of Pf-04518600 as a single agent and in combination with Pf-05082566 in patients with selected locally advanced or metastatic carcinomas | • Part A1—PF-04518600 will be administered IV every 14 days starting at a dose of 0.01 mg/kg, increasing until maximum tolerated dose (MTD) is determined. • Part B1 -PF-04518600 will be administered IV every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered IV 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined |
| NCT02714374 Phase I (recruiting, 2016) | • Eculizumab (C5 neutralizing mab) • GL-ONC1 (vaccinia virus) | Metastatic tumors including MM | Kaitlyn Kelly, MD | An open label, non-randomized Phase 1b study to investigate the safety and effect of the oncolytic virus GL-ONC1 administered intravenously with or without eculizumab prior to surgery to patients with solid organ cancers undergoing surgery for curative-intent or palliative resection | • Arm A: GL-ONC1 escalation dose. • Arm B: GL-ONC1 escalation dose plus eculizumab, single dose on week 1/day 1 at 900 mg 60–90 min prior to GL-ONC1 |