Table 3.
Examples of clinical trials evaluating integrin targeting drugs
| Drug | Target and mechanism | Therapy strategy | NCT# | Clinical phase | Cancer type | Status and Refs |
|---|---|---|---|---|---|---|
| Intetumumab (CNTO 95) | Pan αv-integrin antibody | Alone or in combination with Dacarbazine | NCT00246012 | Phase I/II | Stage 4 melanoma | A nonsignificant trend towards improved OS was observed [93] |
| In combination with docetaxel and prednisone | NCT00537381 | Phase II | Metastatic CRPC | All efficacy end-points favored placebo but not intetumumab, including PFS, tumor response, PSA response, suggesting no beneficial effects [121] | ||
| Abituzumab (EMD 525797) | Pan αv-integrin antibody | In combination with LHRH agonist/antagonist | NCT01360840 | Phase II | Asymptomatic or mildly symptomatic metastatic CRPC | Favorable safety profile and specific activity in PCa–associated bone lesions were observed, but PFS was not significantly extended [94] |
| In combination with cetuximab and FOLFIRI | NCT03688230 | Phase II | KRAS wild-type metastatic CRC with high ανβ6 expression | Withdraw (the primary PFS end point was not met) [95] | ||
| Etaracizumab (MEDI-522 or Vitaxin) | αvβ3 inhibiting antibody | In combination with dacarbazine | NCT00066196 | Phase II | Metastatic melanoma | Terminated due to no clinically meaningful improvement over dacarbazine alone was observed [98] |
| Volociximab | α5β1 inhibiting antibody | Monotherapy | NCT00516841 | Phase II | Platinum-resistant advanced epithelial ovarian or primary peritoneal cancer | Therapy was well-tolerated, but terminated due to lack of efficacy [100] |
| *Cilengitide | RGD peptide mimetic inhibiting αvβ3 and αvβ5 | In combination with Cisplatin, 5-FU, and Cetuximab (PFE combo) | NCT00705016 | Phase I/II | Metastatic HNSCC | Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone [122] |
| In combination with temozolomide (standard chemoradiotherapy) | NCT00689221 | Phase III | Glioblastoma with methylated MGMT promoter | Failed due to no improvement in outcomes, although no additional toxicity was observed [104] | ||
| *ATN-161 | A noncompetitive small peptide inhibitor of β subunits | Monotherapy | Phase I | Advanced solid tumors | Drug was well tolerated but no objective responses were observed [105] | |
| Monotherapy | NCT00131651 | Phase II | Advanced renal cell cancer | Terminated without published clinical results | ||
| *E-7820 | Reducing α2 integrin expression | In combination with Cetuximab | NCT00309179 | Phase II | Metastatic and refractory CRC | Therapy was well-tolerated, but terminated due to lack of efficacy [107] |
| *GLPG0187 | A broad-spectrum integrin receptor antagonist | Monotherapy | NCT01313598 | Phase I | High-grade glioma and other advanced solid tumors | Drug was well tolerated with a dose-proportional pharmacokinetics profile, but failed to show signs of efficacy [108] |
| *MK0429 | Non-peptide small molecule inhibitor of αvβ3 integrin | Monotherapy | NCT00302471 | Phase I | CRPC with bone metastases | Drug was well tolerated and showed early reduction of bone turnover, although PSA was unexpectedly increased during the treatment [109] |
LHRH luteinizing hormone-releasing hormone, CRPC castration-resistant prostate cancer, PSA prostate specific antigen, PCa prostate cancer, PFS progression-free survival, OS overall survival, HNSCC squamous cell carcinoma of the head and neck, CRC colorectal cancer
*Small molecule integrin inhibitor