cd40 agonistic antibody apx005m (sotigalimab) in combination with nivolumab

Conditions: Cancer; Non Small Cell Lung Cancer Metastatic; Metastatic Melanoma; Neoplasm of Lung; Melanoma

Summary: this study is a phase 1-2 open-label dose escalation study of the immuno-activating monoclonal antibody apx005m administered in combination with nivolumab to adult subjects with non-small cell lung cancer or metastatic melanoma. the phase 1 portion is intended to establish the maximum tolerated dose and the recommended phase 2 dose of apx005m when administered in combination with nivolumab. the phase 2 portion of the study will evaluate safety and efficacy of the combination.

apx005m-002 is an open-label phase 1-2 study and comprises a dose-escalation portion (phase 1) followed by a phase 2 tumor specific portion. eligible subjects with non-small cell lung cancer or metastatic melanoma will receive intravenous apx005m in combination with nivolumab until disease progression, unacceptable toxicity or death, whichever occurs first. study objectives include: * determine the maximum tolerated dose and the recommended phase 2 dose of apx005m when given in combination with nivolumab * evaluate safety of the apx005m and nivolumab combination * evaluate the objective response rate, duration of response and median pfs by recist 1.1 in subjects with non-small cell lung cancer or metastatic melanoma receiving apx005m in combination with nivolumab * determine the pk of apx005m

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed, immunotherapy naïve or pd-1/pd-l1 pre-treated, metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment. subjects may be treatment naive or could have received one prior platinum based chemotherapy for non-small cell lung cancer and subjects with a documented activating mutation (e.g., egfr, alk, ros) must also have received the appropriate therapy and progressed * histologically or cytologically confirmed unresectable or metastatic melanoma that progressed during treatment with an anti-pd-1/pd-l1 therapy and had confirmation of pd\>=4 weeks later. subjects with braf activating mutation could have also received a braf inhibitor and/or mek inhibitor regimen prior to anti-pd-1/pd-l1 therapy. * measurable disease by recist 1.1 * ecog performance status of 0 or 1 * adequate bone marrow, liver and kidney function * negative pregnancy test for women of child bearing potential * agreement to use effective methods of contraception per the protocol requirements exclusion criteria: * previous exposure to any immunomodulatory agents (e.g., anti- cd40, anti-pd-1/pd-l1, anti-ctla-4, ido inhibitors) except pd-1/pd-l1 targeting agents in the subsets of patients that must have previous treatment with anti-pd-1/pd-l1 therapy * second malignancy (solid or hematologic) within the past 3 years except locally curable cancers that have been apparently cured * active, known, clinically serious infections within the 14 days prior to first dose of investigational product * use of systemic corticosteroids or other systemic immunosuppressive drugs * active, known or suspected autoimmune disease * history of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis * history of interstitial lung disease * history of life-threatening toxicity related to prior anti-pd-1/pd-l1 treatment for subjects with metastatic melanoma or nsclc.

Keywords: cd40 immunotherapy nivolumab apx005m pd-1