| General information |
| Database: | DB00678 |
| Objective: | A firstinhuman clinical trial of a fully human, Fcengineered IgG1 monoclonal antibody targeting integrin ¦Á5¦Â1 was conducted to evaluate tolerability, maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary antitumor activity. |
| Authors: | Mateo J, et al |
| Title: | A firstinhuman study of the anti¦Á5¦Â1 integrin monoclonal antibody PF04605412 administered intravenously to patients with advanced solid tumors. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2014 |
| PMID: | 25212537 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | PF04605412
|
| Target: | integrin ¦Á5¦Â1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | A first in humanphase I trial study |
| Key Patients Feature: | advancedsolid cancer that has progressed despite currently availabletherapies, Eastern Collaborative Oncology Group (ECOG)Performance Status of 0-1, adequate organ function, absence of brain metastases and no prior history of significant cardiovascular comorbidities, bleeding disorders orvasculitis. Patients on anticoagulant therapy or taking antiplatelet agents were not eligible. Left ventricular ejectionfraction and lung diffusion capacity were tested as part ofthe screening procedures. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm, |
| Treatment Info: | Escalating doses of PF04605412 were given IV on day 1, 28 and every 2 weeks thereafter to patients with advanced solid tumors until disease progression or unacceptable toxicity. Sequential dose cohorts were evaluated based on a modified 3 + 3 doseescalation design. The starting dose was 7.5 mg based on preclinical data. |
| Primary End Point: | DLT, MTD |
| Secondary End Point: | preliminary antitumor activity |
| Patients Number: | 33 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common AEs were fatigue (13 subjects), nausea (10), chills (8) and pyrexia (7). |
| Conclusions: | Based on the safety data, the risks associated with the likelihood of significant cytokinemediated infusion reactions at higher doses, the projected high dose necessary to affect on the biological target and the lack of antitumor activity at the doses explored, the trial was prematurely terminated without determining a formal maximum tolerated dose. Further clinical development of PF04605412 has been discontinued. |