- Preliminary safety and pharmacokinetic data support future Phase 2 studies
NEW HAVEN, CT, USA I May 30, 2015 I Kolltan Pharmaceuticals, Inc. today announced the presentation of interim results from an ongoing Phase 1b study of KTN3379, a human anti-ErbB3 (HER3) monoclonal antibody drug candidate being developed for the treatment of adult patients with advanced solid tumors. The interim results established a recommended Phase 2 dose of KTN3379, demonstrated good tolerability, and showed early signs of activity in combination with other targeted agents. The results were presented in a poster titled “A Phase 1, Open-label Study to Evaluate the Safety and Pharmacokinetics of the Anti-ErbB3 Antibody, KTN3379, Alone or in Combination with Targeted Therapies in Patients with Advanced Tumors” (Abstract #2598, Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics Sat, May 30, 8:00 AM – 11:30 AM CDT, Location: S Hall at the 2015 American Society of Clinical Oncology Annual Meeting in Chicago).
“Targeting ErbB3 for the treatment of multiple types of cancers is an important strategy as ErbB3 participates in tumor survival pathways and may serve as a resistance mechanism for widely-used therapies including agents against other ErbB family members such as HER2 and EGFR,” stated Dr. Todd Bauer of the Sarah Cannon Research Institute in Nashville, TN. “The results for this first-in-human study of KTN3379 demonstrate an acceptable safety profile for further clinical development of the drug candidate and pharmacokinetics consistent with dosing once every three weeks. These data also provide a rationale for Phase 2 investigation of KTN3379 as a novel anti-cancer therapy in combination with other targeted agents.”
“We are delighted with the clinical progress of KTN3379 in that we were able to move quickly from the single agent dose escalation cohorts into combinations based on the safety profile and favorable pharmacokinetic properties shown in this study,” said Dr. Carolyn Sidor, Chief Medical Officer at Kolltan. “The results allow us to plan multiple Phase 2 studies of KTN3379 based on its pharmacokinetics and potentially favorable dosing schedule and what we believe to be its novel binding and dual mechanism of action. Plans are underway to conduct Phase 2 studies in therapeutic combinations in selected solid tumors along with additional Phase 1 studies in head and neck cancer and thyroid cancer beginning this year.”
The ongoing Phase 1b study is a multi-center, open-label, dose escalation study, in which KTN3379 was administered at doses of 5, 10, 15, or 20 mg/kg, or a fixed dose of 1,200 mg, once every three weeks as one hour IV infusions. This was followed by expansion cohorts of six to twelve patients each using 20 mg/kg of KTN3379 in combination with cetuximab, erlotinib, vemurafenib, or trastuzumab. Pharmacokinetic profiling, anti-drug antibodies, pharmacodynamic, and other biomarker analyses were performed.
The ASCO presentation includes the following interim results and data:
- KTN3379 was generally well-tolerated, with diarrhea, rash, and fatigue as the most common treatment-emergent and treatment-related adverse events (all grades). KTN3379 at a dose of 20 mg/kg IV once every three weeks could be combined with other targeted therapies including small molecules and biologics;
- Pharmacokinetic results indicated a dose-proportional increase in levels of KTN3379 over the dose range evaluated and exceeded the target trough levels at which anti-tumor activity was observed in preclinical models, ultimately supporting a recommended Phase 2 dose of 15 mg/kg;
- The pharmacokinetic profile of KTN3379 in combination was not significantly different from single-agent results and supports planning of Phase 2 trials;
- Pharmacodynamic biomarker analyses showed that soluble circulating ErbB3 levels were increased in all patients at all doses, indicating that KTN3379 binds ErbB3, and is not influenced by combination treatment; and
- Efficacy assessment is ongoing and stable disease was reported in several patients treated with combinations of KTN3379 and cetuximab, trastuzumab, or vemurafenib. Seven patients have yet to reach their initial tumor re-evaluation time-point which is anticipated in the next few months.
About KTN3379
KTN3379 is a human monoclonal antibody designed to block the activity of ErbB3 (HER3), an RTK that belongs to the epidermal growth factor receptor, or EGFR, family. ErbB3 is believed to be an important receptor regulating cancer cell growth and survival. ErbB3 is expressed in many cancers including head and neck, breast, lung, gastric and melanoma. While there are several successful currently marketed products targeting two members of the EGFR family, there are none that directly target ErbB3. In cancer, ErbB3 activation can be driven by its ligand, neuregulin (NRG), or in its absence, through overexpression of its co-receptor ErbB2 (HER2).
About Kolltan Pharmaceuticals
Kolltan, a privately held clinical-stage company, is focused on the discovery and development of novel antibody-based drugs targeting receptor tyrosine kinases for the treatment of cancer and other diseases with significant unmet need. Kolltan’s founders and members of its management team have deep expertise and a proven track record in drug discovery, development and commercialization of innovative therapeutics, including drugs targeting kinases. Kolltan is working in close collaboration with the laboratory of Kolltan Co-Founder, Dr. Joseph Schlessinger, as well as the Yale University medical and scientific community. The Company has a broad and novel portfolio of therapeutic biologics targeting multiple receptor tyrosine kinases that are advancing in clinical and preclinical development and are expected to generate multiple near-term milestones.
SOURCE: Kolltan Pharmaceuticals
