Table 2. Recent updates on ongoing immunotherapy clinical trials.
| Study name/identifier | Conference/year | Medication | Disease | Setting | Phase/population size reported | Outcomes |
|---|---|---|---|---|---|---|
| NCT02715531 (23,24) | ESMO/2018 | Atezolizumab 1,200 mg + bevacizumab 15 mg/kg q3w | HCC | Unresectable or metastatic, first-line‡ | Phase Ib/68 | ORR 34%; CR 1%; DCR 78%; mPFS 14.9 mos; mOS NR; grade 3–5 TRAEs 25% |
| NCT03289533 (25,26) | ASCO/2019 | Avelumab 10 mg/kg q2w + axitinib 5 mg PO BID | HCC | Locally advanced or metastatic, first-line† | Phase Ib/22 | RECIST: ORR 13.6%; mPFS 5.5 mos |
| mRECIST: ORR 31.8%; mPFS 3.8 mos | ||||||
| Grade 3 TRAEs: HTN 50%; HFS 22.7%; no grade 4–5 TRAEs | ||||||
| Grade 3 irAEs: hypothyroidism 31.8%; hyperthyroidism 13.6% | ||||||
| No discontinuation due to TRAEs/irAEs | ||||||
| NCT02989922 (27,28) | ESMO/2018 | Camrelizumab 3 mg/kg q2w or q3w | HCC | Advanced, second-line or later‡ | Phase II/220 Chinese patients only | ORR 13.8%; DCR 44.7%; mDOR NR; mPFS 2.1 mos; mOS NR; 6-mo OS: 74.7%; grade 3–5 TRAEs 19.4% |
| NCT03092895 (29,30) | ASCO/2019 | Camrelizumab 3 mg/kg q2w + FOLFOX4 or GEMOX | HCC | Advanced, first-line‡ | Phase II/34 Chinese patients only | ORR 26.5%; DCR 79.4%; mPFS 5.5 mos; mOS NR; grade 3–5 irAEs 5.9% |
| BTC | Phase II/47 Chinese patients only | ORR 7.0%; DCR 67.4%; mPFS & mOS NR; grade 3–5 irAEs 3.8% | ||||
| NCT03486678 (31,32) | ASCO/2019 | Camrelizumab 3 mg/kg q2w + GEMOX | BTC | Advanced, first-line | Phase II/26 | ORRs: GBC 63.64%; CCA 33.33% |
| NCT02383212 (33,34) | ESMO/2018 | Cemiplimab 3 mg/kg q2w | HCC | Advanced, second-line | Phase I/26 | ORR 19.2%; DCR 73%; mPFS 3.7 mos; TEAE related-deaths 7.7% |
| ESMO Immuno-Oncology/2018 | ||||||
| NCT01693562 (35,36) | ASCO/2017 | Durvalumab 10 mg/kg q2w for 12 mos | HCC | Locally advanced, unresectable, or metastatic, second-line or later† | Phase I/II, 40 | Overall: ORR 10.3%; DCR 33.3%; mOS 13.2 mos; grade 3–4 TRAEs 20.0% |
| HCV+ (8 pts): ORR 25.0%; DCR 62.5%; mOS 19.3 mos | ||||||
| HBV+ (9 pts): ORR 0%; DCR 11.1%; mOS 6.3 mos | ||||||
| NCT02519348 (37-39) | ASCO/2017 | Durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w for 4 doses followed by durvalumab 20 mg//kg q4w | HCC | Advanced, second-line or later | Phase I/40 | Overall: ORR 15%; DCR 57.5% (16 weeks); grade 3–5 TRAEs 20% (no TR deaths) |
| Uninfected (20 pts): ORR 30%; DCR 70% | ||||||
| HBV+ (11 pts): ORR 0%; DCR 45.5% | ||||||
| HCV+ (9 pts): ORR 0%; DCR 44.4% | ||||||
| NCT02821754 (40,41) | ASCO/2019 | Durvalumab 1,500 mg + tremelimumab 75 mg monthly for 4 doses followed by durvalumab 1,500 mg monthly | HCC | Advanced, second line or later‡ | Phase II/10 | ORR 20%; DCR 60%; mPFS 7.8 mos; mOS 15.9 mos |
| BTC | Phase II/12 | ORR 0%; DCR 41.7%; mPFS 3.1 mos; mOS 5.45 mos | ||||
| NCT02572687 (42,43) | ASCO/2019 | Durvalumab 750 mg + ramucirumab 8 mg/kg q2w | HCC | Locally advanced, unresectable, or metastatic, second-line or later† | Phase Ib/28 | Overall: ORR 11%; DCR 61%; mDOR NR; mPFS 4.4 mos; mOS 10.7 mos |
| PD-L1 ≥25%: ORR 18%; DCR 73%; mPFS 5.6 mos; mOS 16.5 mos | ||||||
| NCT02829918 (44,45) | ASCO/2019 | Nivolumab 240 mg IV q2w for 16 weeks, then 480 mg IV q4w | BTC | Advanced, second-line or later† | Phase II/54 | PR 22%; DCR 60%; mPFS 3.98 mos; mOS 14.22 mos; grade 3–5 irAEs 20% |
| NCT03222076 (46,47) | ASCO/2019 | Nivolumab 240 mg q2w for 6 weeks or nivolumab 240 mg q2w + ipilimumab 1 mg/kg q6w for 6 weeks | HCC | Pre-operative, resectable† | Phase II/14 | pCR rate 29%; grade 3–5 TRAEs 34% |
| NCT01658878 CheckMate-040 (13,48) | ASCO/2019 | Nivolumab + ipilimumab (variable dosage regimens) | HCC | Advanced, second-line‡ | Phase Ib/148 | ORR 31%; CR 5%; DCR 54%; mDOR 17 mos; mOS 22.8 mos; grade 3–5 TRAEs 34% (5% leading to discontinuation) |
| NCT02576509 CheckMate-459 (49,50) | N/A, BMS press release/2019 | Nivolumab vs. sorafenib | HCC | Advanced, unresectable, first-Line† | Phase III/1,009 (planned enrollment, total studied not reported) | OS HR =0.85 (95% CI: 0.72–1.02) P=0.0752 (NS) |
| No new safety signals | ||||||
| NCT02702401 KEYNOTE-240 (21,22) | ASCO/2019 | Pembrolizumab 200 mg q3w vs. placebo | HCC | Advanced, second-line† | Phase III/413 | ORR 16.9%; mDOR 13.8 mos; OS (HR =0.78); PFS (HR =0.78) |
| NCT02054806 (KEYNOTE-028) (51,52) | ASCO/2019 | Pembrolizumab 10 mg/kg q2w | BTC | Advanced, later line | Phase I/24 pts with PD-L1+ (≥1%) tumors | ORR 13.0%; mPFS 2.0 mos; mOS 7.4 mos; irAEs 20.8% |
| NCT02628067 (KEYNOTE-158) (51,53) | ASCO/2019 | Pembrolizumab 200 mg q3w | BTC | Advanced, later line | Phase II/104 (61 pts with PD-L1+ tumors) | ORR 5.8%; mPFS 1.8 mos; mOS 6.2 mos; irAEs 18.3% |
| NCT03006926 KEYNOTE-524 (54,55) | ASCO/2018 | Pembrolizumab 200 mg q3w + lenvatinib (8 or 12 mg/day weight-based) | HCC | Unresectable, first-line† | Phase Ib/18 | ORR 46%; DCR 92%; No DLTs, 94% TEAEs |
†, Child Pugh A Only; ‡, Child Pugh A or B7. TEAEs, treatment-emergent adverse events; GBC, gallbladder cancer; CCA, cholangiocarcinoma; DLT, dose-limiting toxicities; NS, not significant; HCC, hepatocellular carcinoma; BTC, biliary tract cancer; ORR, objective response rate; CR, complete response; DCR, disease control rate; mPFS, median progression-free survival; mOS, median overall survival; pts, patients; TRAEs, treatment-related adverse effects; irAEs, immune-related adverse events; mDOR, median duration of response; HCV, hepatitis C virus; HBV, hepatitis B virus; pCR, pathologic CR; HR, hazard ratio; CI, confidence interval; TR, treatment-related; HTN, hypertension; HFS, hand-foot syndrome.