Phase IB trial of oral talactoferrin in the treatment of patients with metastatic solid tumors

Abstract

Purpose: We evaluated safety and activity of talactoferrin, a novel immunomodulatory protein in a phase IB trial of patients with refractory solid tumors. Methods: Thirty-six patients with metastatic cancer who had progressed on, or were ineligible for, standard chemotherapy received single-agent oral talactoferrin. Following doseescalation, with no DLTs , patients were randomized to 4.5 or 9 g/day talactoferrin. Results: Talactoferrin was well tolerated with apparent anti-cancer activity, particularly in NSCLC and RCC. One patient had a PR (RECIST) and 17 patients (47%) had stable disease (50% disease control rate). Median PFS in the twelve NSCLC and seven RCC patients was 4.2 and 7.3 months, respectively. There was no apparent difference in anti-tumor activity or adverse events between talactoferrin doses. Conclusions: Oral talactoferrin was well tolerated. Although evaluated in a small number of patients, talactoferrin appeared to have anti-cancer activity, particularly in NSCLC and RCC and should be evaluated further.

Plant‐based biopharming of recombinant human lactoferrin

“…Apart from its main physiological functions, namely binding and transport of iron ions, Lf exhibits antiviral, antimicrobial, antiprotozoal and antioxidant activities. Moreover, recombinant Lf has been tested for clinical use in treatment and prevention of such human and animal diseases as solid tumors (Hayes et al, 2005(Hayes et al, , 2010 and diarrhea (Humphrey et al, 2002). Pepsin digestion of Lf generates its fragment lactoferricin (Bellamy et al, 1992) that also reveals potent bactericidal activity against antibiotic-resistant strains of Staphylococcus aureus and Escherichia coli from clinical origins (Flores-Villaseñor et al, 2010).…”

“…Pepsin digestion of Lf generates its fragment lactoferricin (Bellamy et al, 1992) that also reveals potent bactericidal activity against antibiotic-resistant strains of Staphylococcus aureus and Escherichia coli from clinical origins (Flores-Villaseñor et al, 2010). Moreover, recombinant Lf has been tested for clinical use in treatment and prevention of such human and animal diseases as solid tumors (Hayes et al, 2005(Hayes et al, , 2010 and diarrhea (Humphrey et al, 2002). Its use as vaccine adjuvant modulates the adaptive immune response in humans (Hwang et al, 2011).…”

“…In spite of the large list of rLf expressing systems, only a few have been approved for the market and/or introduced in clinical practice. For instance, Aspergillus niger-produced Lf (trade nametalactoferrin) (Ward et al, 1995) is used for solid tumors treatment (Hayes et al, 2005(Hayes et al, , 2010 and Oryza sativa-derived Lf (trade namelacromin) is an antiapoptotic cell culture media supplement that increases cell growth rate (InVitria, Ventria Bioscience, USA, http://www. invitria.com).…”

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

“…In a followup phase IB trial, TLf was again well-tolerated by patients with metastatic cancer. NSCLC patients (n=12) experienced 87% relative reduction in TGR and renal cell carcinoma (RCC) patients (n = 7) experienced a 98% relative reduction in TGR [84]. In a phase 2 clinical trial of TLf in RCC, Jonasch et al [85] reported that TLf given at a dose of 1.5 g twice daily (12 weeks on, 2 weeks off) resulted in no toxicities to 44 patients with RCC, 6.4 months mPFS, 21.1 months median overall survival, and a 77% 1-year survival rate.…”

Talactoferrin Immunotherapy in Metastatic Renal Cell Carcinoma: A Case Series of Four Long-Term Survivors

“…In a phase IB trial [13] and a follow-on phase II study [14], 16 patients with metastatic RCC, all with documented tumor progression during the 9 months prior to enrollment, were treated at our institution with single-agent oral talactoferrin. Patients received oral rhLF in amounts of 4.5 grams or 9 grams per day administered in two divided doses.…”