Table 4.
Clinical trials associating anti-TRAIL-R2 antibodies and chemotherapy
| Combination | Phase | Pts n (=) | Tumour | Safety | Best response | Reference |
|---|---|---|---|---|---|---|
| Conatumumab | ||||||
| Ganitumab (or AMG 479) | I | 9 | Advanced, refractory solid tumours | Safe with AMG 479 up to 15 mg·kg−1 | SD (3) | NCT00819169 Chawla et al., 2010 |
| Doxorubicin | II R | 128 | Unresectable soft tissue sarcomas | Safe with doxorubicin up to 15 mg·kg−1 Not better than doxorubicin alone | ORR decreased versus placebo 20 versus 24% | NCT00626704 Demetri et al., 2012 |
| mFOLFOX6 and Bevacizumab | Ib/2 | 202* | First-line mCRC | NR | Ongoing, not recruiting | NCT00625651 |
| FOLFIRI or ganitumab + FOLFIRI | II R | 155 | Second-line treatment mutant KRAS mCRC | CON+F tolerable in this population CON + F improved PFS | ORR was increased versus placebo 14 versus 2% | NCT00813605 Cohn et al., 2012 |
| Gemcitabine or gemcitabine + AMG 479 | II R | 125 | Metastatic pancreatic cancers | Safe with gemcitabine up to 10 mg·kg−1 | Some activity PR (1) SD (22) | NCT00630552 Kindler et al., 2010 |
| Carboplatin and paclitaxel | Ib/2 | 172* | First-line advanced NSCLC | NR | Completed | NCT00534027 |
| Panitumumab | Ib/2 | 53* | mCRC | NR | NR | NCT00630786 |
| Bortezomib or vorinostat | Ib | 62* | Relapsed or refractory lymphomas | NR | Suspended | NCT00791011 |
| Drozitumab | ||||||
| Rituximab | II | 40 | Relapsed NHL | Safe with rituximab up to 15 mg·kg−1. Not better than rituximab alone | CR (2) PR (18) | NCT00517049 Wittebol et al., 2010 |
| Carboplatin, paclitaxel ± bevacuzimab | II R | 124 | Previously untreated stage IIIb, IV NSCLC | The results do not support further evaluation with PC ± B | Similar to PC ± B alone | Karapetis et al., 2010 |
| Cetuximab and irinotecan or FOLFIRI ± bevacuzimab | Ib | 20 | First-line mCRC | Safe with irinotecan-regimens up to 15 mg·kg−1 | PR (3*) SD (13) | NCT00497497 Baron et al., 2011 |
| FOLFOX ± bevacuzimab | Ib | 9 | First-line mCRC | The results do not support further evaluation with FOLFOX ± B | PR (5*) SD (3) | NCT00851136 Rocha Lima et al., 2011; 2012 |
| LBY135 | ||||||
| Capecitabine | I | 24 | Advanced solid tumours | Tolerated with capecitabine at 20 mg·kg−1 but 2 grade 3 DLTs observed at 1 and 20 mg·kg−1 | Some activity PR (1) – two pts with decreased tumour vol. 60–73% | Sharma et al., 2008 |
| Lexatumumab | ||||||
| Gemcitabine, pemetrexed, doxorubicin or FOLFIRI | Ib | 41 | Advanced solid tumours | Tumour shrinkage observed, confirmed PRs in the FOLFIRI and doxorubicin arms | NR | Sikic et al., 2007 |
| IFNγ | I | 19 | Refractory paediatric solid tumours | NR | NCT01445093 | |
| Tigatuzumab | ||||||
| Carboplatin, paclitaxel | II R | 109* | Metastatic or unresectable NSCLC | NR | Completed | NCT00991796 |
| II | 24 | Locally advanced or metastatic ovarian cancer | NR | Completed | NCT00945191 | |
| Gemcitabine | II | 65* | Untreated and unresectable pancreatic cancer | NR | Completed | NCT00521404 |
| Irinotecan | II R | 8* | mCRC failed first-line treatment with oxaliplatin | NR | Completed | NCT00969033 |
| FOLFIRI | I | 20* | Patients who have failed other treatments | NR | Ongoing, not recruiting | NCT01124630 |
| Sorafenib | II R | 160* | Advanced liver cancer | NR | Ongoing, not recruiting | NCT01033240 |
| Abraxane (paclitaxel) | II R | 60* | Metastatic triple negative breast cancer | NR | Ongoing, not recruiting | NCT01307891 |
*
Estimation/expected.
CR, complete response; CRC, colorectal cancer; DLT, dose-limiting toxicity; FOLFIRI, folinic acid, fluorouracil, irinotecan; FOLFOX, folinic acid, fluorouracil, oxaliplatin; mCRC, metastatic colorectal carcinomas; NHL, non-Hodgkin lymphoma; NR, not reported; NSCLC, non-small cell lung carcinoma; ORR, objective response rate; PCB, paclitaxel, carboplatin, bevacizumab; PR, partial response; pts, patients; R, randomized; SD, stable disease.