Table 2.
Ongoing phase I–II trials investigating immunotherapy and tyrosine kinase inhibitor combination therapy regimens for advanced, unresectable, or locally advanced HCC
| Study name/identifier | Trial setting (first/second line) | Patient population | Design (interventions) | Primary endpoint(s) | Study type | Planned enrollment, n |
|---|---|---|---|---|---|---|
| NCT03006926 | First line | Histologically confirmed HCC with no other appropriate treatment available; no prior systemic therapy (for the expansion part) | Lenvatinib + pembrolizumab | Dose escalation: number of patients with AE (serious and nonserious); DLT of lenvatinib and pembrolizumab in cycle 1 Dose expansion: ORR and DOR | Phase Ib (dose escalation and dose expansion) | 104 |
| NCT03170960 | First line | Locally advanced or metastatic solid tumors including HCC; no prior systemic therapy | Cabozantinib + atezolizumab | Dose escalation: maximum tolerated dose Dose expansion: ORR | Phase Ib (dose escalation and dose expansion) | 1,000 (across all tumor types) |
| NCT03418922 | First line | Histologically confirmed HCC with (part 1) no other appropriate treatment available or (part 2) no prior systemic therapy | Lenvatinib + nivolumab | Part 1: number of patients with DLT Part 2: number of patients with AE (serious and nonserious) | Phase Ib (part 1 and part 2) | 26 |
| NCT03347292 | First line | Advanced HCC (BCLC stage B or C) with no prior systemic therapy | Regorafenib + pembrolizumab | Incidence and severity of treatment-emergent AE; DLT | Phase Ib (dose escalation and dose expansion) | 40 |
| NCT03439891 | First line | Unresectable, locally advanced, or metastatic HCC; no prior systemic therapy | Nivolumab + sorafenib Lead-in arm 1: nivolumab (from day 1 onward), sorafenib (from day 15 onward) | Lead-in arm 2: sorafenib (from day 1 onward), nivolumab (from day 15 onward) Maximum tolerated dose; overall response rate | Phase II (dose escalation and expansion) | 40 |
| CheckMate 040/NCT01658878a | First/second line | Histologically confirmed advanced, unresectable HCC Treatment naïve or progressive disease after sorafenib | Combination arms in this trial: nivolumab + ipilimumab, nivolumab + cabozantinib, and nivolumab + ipilimumab + cabozantinib | Safety/tolerability (incidence of AE, serious AE, discontinuations, deaths, and clinical laboratory test abnormalities); ORR | Phase I/II (dose escalation and dose expansion) | 620 |
| NCT02423343 | Second line | Recurrent HCC; progression on prior sorafenib or intolerant to sorafenib For phase II: AFP ≥ 200 ng/mL | Galunisertib + nivolumab | Phase Ib: maximum tolerated dose | Phase Ib/II (dose escalation and cohort expansion) | 75 |
| NCT02572687 | Second line | Locally advanced, unresectable, or metastatic gastrointestinal or thoracic malignancies, including HCC; patients should have disease progression with prior sorafenib or intolerance to prior sorafenib and AFP ≥ 1.5 × the upper limit of normal | Ramucirumab + MEDI4736 | Number of patients with DLT | Phase I | 114 |
| REGOMUNE/NCT03475953 | Second line | Advanced digestive tumors including unresectable/metastatic hepatobiliary cancers; must have received ≥ 1 prior systemic therapy | Regorafenib + avelumab | Part 1: recommended phase II dose of regorafenib Part 2: assessment of objective response as per RECIST v1.1 | Phase I/II (part 1 and part 2) | 212 |
| NCT03299946 | Neoadjuvant | Locally advanced HCC | Neoadjuvant cabozantinib + nivolumab (CaboNivo) followed by definitive resection | Number of AE; number of patients who complete preoperative treatment and proceed to surgery | Phase Ib | 15 |
| NCT03713593 | First line | Confirmed HCC; BCLC stage B not amenable to curative or locoregional therapy/stage C; no prior systemic treatment | Lenvatinib + pembrolizumab/placebo | PFS as per RECIST 1.1 by BICR; OS | Phase III | 750 |
AE, adverse events; AFP, alpha-fetoprotein, BCLC, Barcelona Clinic Liver Cancer; BICR, blinded independent central review; DLT, dose-limiting toxicities; DOR; duration of response; HCC, hepatocellular carcinoma; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors.
a
Other arms include: nivolumab monotherapy in uninfected, hepatitis C virus-infected, and hepatitis B virus-infected patients; nivolumab vs. sorafenib as a comparator arm; and nivolumab monotherapy in patients with Child-Pugh B.