Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects

The purpose of this study is to evaluate the safety and efficacy of ALD518 in modifying the course of oral mucositis in subjects with head and neck cancer receiving concomitant chemotherapy and radiotherapy

This was a Phase 2, placebo-controlled, double-blind study in subjects newly diagnosed with head and neck cancer (who had not received previous treatment for oral mucositis) and who were receiving concomitant chemotherapy and radiotherapy. Subject eligibility, including tumor staging, was assessed during the screening period, which was to occur within 30 days prior to the initiation of radiation therapy. The radiation therapy treatment period was approximately 7 weeks, depending on the subject's prescribed radiation plan. Prior to the randomized portion of the trial, the first 7 subjects enrolled in the study entered a safety run-in evaluation and received a total of 2 doses of open-label clazakizumab 160 mg IV, 4 weeks apart (Day 0 and Week 4 of radiation); these subjects were not eligible for the randomized portion of the study. Subsequent to completion of the safety run-in, eligible subjects were randomized 1:1:1 to treatment with 2 doses of clazakizumab 160 mg, or clazakizumab 320 mg, or placebo, administered IV 3 weeks apart (Day 0 and Week 3 of radiation therapy). All subjects were to be followed for 4 weeks post last day of radiotherapy treatment for the primary efficacy and safety assessments and then for up to an additional 12 months of long-term follow-up.

Eligibility Criteria:
Inclusion Criteria:

* Have recently diagnosed (\< than 6 months prior to screening visit date), pathologically confirmed, non-metastatic SCC of the oral cavity, oropharynx, hypopharynx or larynx that will be treated with CRT as first-line treatment; subjects with a history of surgical management (approximately 4-6 weeks before RT with sufficient time for post-surgical healing) are eligible
* Have a plan to receive a continuous course of conventional external beam irradiation delivered by intensity-modulated radiotherapy (IMRT) as single daily fractions of 2.0 to 2.2 Gy, with a cumulative radiation dose between 55 and 72 Gy.
* Have a plan to receive a standard cisplatin CT regimen administered tri-weekly (80 to 100 mg/m2, on Days 0, 21, and 42) or weekly (30 to 40 mg/m2) or a standard carboplatin regimen administered weekly (100 mg/m2)
* Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* CRP \< 80 mg/L
* Have adequate hematopoietic, hepatic, and renal function at the screening visit

Exclusion Criteria:

* Tumor of the lips, sinuses, salivary glands, nasopharynx or unknown primary tumor
* Metastatic disease (M1) Stage IV C
* Any prior history of head and neck cancer
* Prior radiation to the head and neck
* Have had a major surgical procedure, other than for HNC, or significant traumatic injury within 4 weeks prior to the initiation of RT; or anticipation of need for a major surgical procedure during the clinical trial
* Active infectious disease, excluding oral candidiasis
* Have OM at the screening visit
* Have a history of hypersensitivity to monoclonal antibody