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Table 3 Examples of clinical trials evaluating integrin targeting drugs

From: Integrins regulate stemness in solid tumor: an emerging therapeutic target

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]
  1. 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
  2. *Small molecule integrin inhibitor