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Background: An abbreviated pathway for biological products shown to be biosimilar to the reference product exists in Europe and the US. The randomized PROTECT1 trial compared the efficacy and safety of the proposed biosimilar pegfilgrastim with reference pegfilgrastim. Methods: In this multinational, prospective, double-blind trial, chemotherapy-naïve women aged ≥18 years with histologically proven breast cancer received up to 6 cycles of (neo)-adjuvant TAC chemotherapy (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2). Patients were randomized to a single 6 mg SC injection of the proposed biosimilar pegfilgrastim (LA-EP2006) or the reference (Neulasta®) on day 2 of each cycle. Primary endpoint was duration of severe neutropenia (DSN) during Cycle 1, defined as number of consecutive days with an absolute neutrophil count (ANC) Results: A total of 316 patients were randomized and included in the full analysis set (LA-EP2006: n=159; reference: n=157). Baseline demographics were similar in both groups (mean±SD age: LA-EP2006 49.9±9.53, reference 50.5±10.87 years; breast cancer stage II-III: LA-EP2006 n=155 [97.5%], reference n=151 [96.2%]). Mean±SD DSN in Cycle 1 was 0.75±0.88 days with LA-EP2006 and 0.83±0.90 days with reference, with a treatment difference of 0.07 days (95% CI: −0.12, 0.26); LA-EP2006 was both equivalent and non-inferior to the reference. There were no clinically meaningful differences between LA-EP2006 and reference in incidence of febrile neutropenia (3.8% vs 7.0% in Cycle 1, 5.7% vs 7.6% across all cycles), days with fever, depth of ANC nadir in Cycle 1, time to ANC recovery in Cycle 1, or frequency of infections in Cycle 1 and across all cycles. Treatment-emergent adverse events (TEAEs) were similar across groups and consistent with the known safety profile of pegfilgrastim. Most frequently reported TEAEs related to treatment were musculoskeletal and connective tissue disorders (LA-EP2006 4.4%, reference 5.7%). Serious TEAEs were reported in 10.1% of LA-EP2006 and 13.4% of reference patients. No neutralizing anti-pegfilgrastim antibodies were detected. Conclusions: Proposed biosimilar pegfilgrastim (LA-EP2006) met the primary endpoint demonstrating both equivalence and non-inferiority to the reference. LA-EP2006 and the reference are similar with no clinically meaningful differences regarding efficacy and safety in breast cancer patients receiving (neo)-adjuvant myelosuppressive chemotherapy. Citation Format: Harbeck N, Zbarskaya I, Lipatov O, Frolova M, Udovitsa D, Topuzov E, Ganea-Motan DE, Nakov R, Singh P, Rudy A, Blackwell K. A randomized, double-blind trial to compare the efficacy and safety of proposed biosimilar pegfilgrastim (LA-EP2006) with reference pegfilgrastim in patients with breast cancer (PROTECT1). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-01.

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Background The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. Patients and methods Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. Results Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2–34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). Conclusion No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. Clinical Trial Number NCT00851084, www.clinicaltrials.gov , EudraCT 2008-004178-41.