Date: 2016-07-01
Type of information: Publication of results in a medical journal
phase: 2-3
Announcement: publication of results in Clinical Cancer Research
Company: Active Biotech (Sweden)
Product: ANYARA (naptumomab estafenatox)
Action
mechanism: fusion protein/immunotherapy product. ANYARA is an immunoconjugate. This fusion protein consists of one antigen binding fragment (Fab moiety of a monoclonal antibody recognizing the tumor-associated oncofetal trophoblast glycoprotein antigen 5T4) from a cancer cell binding antibody and a bacterial superantigen. The first one recognizes tumor cells and the latter is thought to bind T lymphocytes, so that the fusion protein can stimulate them to attack and kill the tumor cells recognized by the antibody part of this targeted drug.
The development of ANYARA is mainly focused on renal cell cancer. The product has been gratend orphan status in the EU for the treatment of renal cell carcinoma on 14 September 2007 (EU/3/07/480). Positive data was reported from clinical Phase I trials in lung cancer, renal cell cancer and pancreatic cancer. In July 2009, the results from two Phase I studies of ANYARA were published in the Journal of Clinical Oncology, where ANYARA was studied both as a single agent (monotherapy) and in combination with an established tumor therapy - docetaxel (Taxotere®) - in patients with advanced cancer. The results showed that ANYARA was well tolerated both as monotherapy and in combination with docetaxel.
Disease: renal cell cancer
Therapeutic area: Cancer - Oncology
Country: UK, Bulgaria, Russia, Romania, Ukraine
Trial
details: The Phase II/III study was designed to evaluate the effect of ANYARA in combination with interferon-alpha, compared with interferon-alpha alone, in patients with advanced renal cell cancer. The primary endpoint was overall survival (OS). In May 2008, a positive interim analysis of safety and efficacy was performed and the study continued into the Phase III part. Enrollment of 513 patients was completed in June 2009 and recruited patients from approximately 50 sites in Europe (UK, Ru, Uk, Bu, Ro). Secondary endpoints in the study were Progression Free Survival (PFS) and safety. (NCT00420888)
Latest
news: * On July 1, 2016, results of a randomized phase II/III Study of naptumomab estafenatox + IFNalpha versus IFNalpha in renal cell carcinoma have been published in Clinical Cancer Research. In this randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 µg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s.c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). The study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). * On June 3, 2013, Active Biotech has presented overall survival (OS) and Progression Free Survival (PFS) data from the ANYARA Phase II/III study in renal cell cancer at the 2013 ASCO Annual Meeting. The study encompassed 513 patients and was designed to evaluate the effect of ANYARA (naptumomab estafenatox) in combination with interferon-alpha, compared with interferon-alpha alone, in patients with advanced renal cell cancer. The primary endpoint was overall survival (OS).
The results showed that although the ANYARA Phase II/III study did not achieve its primary endpoint to show a prolonged OS in the overall ITT population, the addition of ANYARA to interferon-alpha improves OS and PFS in a biomarker defined subgroup. In this subgroup, patients with high levels of pre-formed antibodies against superantigens or the cytokine IL-6 were excluded. High baseline levels of these antibodies were shown to decrease ANYARA levels while the biomarker IL-6 has previously been suggested to be a predictive marker for immune therapies. In this subgroup of 130 patients, the median OS for the ANYARA vs. placebo treatment arm were 63.3 vs. 31.1 months (HR: 0.59; p=0.020), respectively. The median PFS were 13.7 (ANYARA) vs. 5.8 (placebo) months (HR: 0.62; p=0.016).
To test the robustness of these data, an alternative subgroup of 131 patients, based on previously published cut-off levels of these biomarkers, was investigated. In this subgroup, the median OS for ANYARA in combination with interferon-alpha versus interferon-alpha alone were 30.4 and 21.7 months (HR=0.65, (p=0.036), respectively. The median PFS of ANYARA in combination with interferon-alpha versus interferon-alpha alone were 8.5 and 5.8 months (HR=0.75, p=0.162), respectively.
Active Biotech is now seeking a partner for the continued development of ANYARA.
* On January 28, 2013, Active Biotech has announced the initial results from the ANYARA Phase II/III clinical study. The study encompassed 513 patients and was designed to evaluate the effect of ANYARA in combination with interferon-alpha, compared with interferon-alpha alone, in patients with advanced renal cell cancer. The primary endpoint was overall survival (OS).
The results showed that the ANYARA Phase II/III study did not achieve its primary endpoint to show a prolonged OS in the ITT population. Unexpectedly, and in contrast to previous studies in other territories, a majority of the patients in the current study had high levels of pre-formed antibodies against the superantigen component of ANYARA. A subgroup analysis, excluding patients with high levels of pre-formed antibodies, resulted in a trend for survival benefit with ANYARA treatment. Furthermore, baseline levels of the biomarker IL-6 was shown to be an important predictive marker for a positive treatment effect of ANYARA.
In a hypothesis generating subgroup analysis, the 25 % of patients with low/normal levels of base line IL-6 and expected anti-superantigen antibody levels, showed a statistically significant treatment advantage on both OS (p=0.02, HR=0.59) and PFS. In North America and Western Europe, this subgroup account for 40-50% of the total number of advanced renal cell cancer patients. The trial showed that there is a treatment effect in a significant subgroup of patients. This observation is congruent with ANYARAs mode of action. Active Biotech will seek a partner for the continued development of this unique, targeted, immune therapy.
The safety profile was good and in line with previous observations; the most common adverse events associated with ANYARA treatment were grade 1-2 fever, nausea or vomiting. No new and unexpected safety concerns were identified in the study.
Additional analyses of the ANYARA Phase II/III study data are ongoing, and results will be submitted for presentation at a scientific congress later in the year. The company will also discuss future development strategies with major regulatory authorities.
