CD40 Agonistic Antibody APX005M (Sotigalimab) in Combination With Nivolumab

Apexigen America, Inc.140 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

140

Conditions

Cancer Non Small Cell Lung Cancer Metastatic

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (23)

University of Arizona Cancer Center

Tucson, Arizona, United States

City of Hope

Duarte, California, United States

Yale University

New Haven, Connecticut, United States

Hem-Onc Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC)

Baltimore, Maryland, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

SUNY Upstate Medical Hospital

Syracuse, New York, United States

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, United States

...and 13 more locations

Outcomes

Primary Outcomes

Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

All toxicities were graded according to the NCI-CTCAE version 4.03. DLT was defined as any of the following events attributed to APX005M and nivolumab combination: * Grade 4 hematologic toxicity lasting ≥ 7 days (except asymptomatic lymphopenia) * Grade 3 or 4 neutropenia with a single temperature of \>38.3◦ C (101◦ F) or a sustained temperature of ≥38◦ C (100.4◦ F) for more than one hour * Grade 4 thrombocytopenia or Grade ≥3 thrombocytopenia with signs or symptoms of bleeding or requiring platelet transfusion * Grade 4 non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting \>3 days despite optimal supportive care * Any Grade ≥ 3 non-hematologic laboratory value if: medical intervention is required to treat the subject, abnormality leads to hospitalization, or abnormality persists for \>1 week * Failure to recover from a treatment-related AE to baseline or ≤ Grade 1 within 12 weeks of last dose of investigational product * Grade 5 toxicity.

Time frame: Up to 21 days following first dose of APX005M and nivolumab

Maximum Tolerated Dose (MTD) of APX005M + Nivolumab (Phase 1b)

Establish the MTD dose of APX005M combined with 360 mg of nivolumab for which for which \< 33% of DLT- evaluable participants experience a DLT. In Phase 1b, the RP2D was based on the overall safety and tolerability of the combination of APX005M and nivolumab by testing increasing doses up to 0.3 mg/kg APX005M + nivolumab.

Time frame: Up to 21 days following first dose of APX005M and nivolumab

Phase 2 Evaluate the Objective Response Rate (ORR) by RECIST 1.1 and iRECIST in Each Cohort / Group

ORR defined as the rate of patients who show as best overall response; either a complete response (CR) or a partial response (PR). The ORR can be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. using computed tomography (CT) scans/magnetic resonance imaging (MRI). Per RECIST v1.1, for target lesions and assessed by imaging: Complete Response, (CR), Disappearance of all target lesions and nontarget (NT) lesions; Partial Response (PR), \>30% decrease in the sum of the longest diameter of target lesions and no PD in NT lesions or new lesions; Objective Response Rate (ORR)=CR + PR.

Time frame: From start of the treatment (Day 1) until disease progression, withdrawal of consent, death, initiation of any anticancer therapy, lost to follow-up, or termination by the Sponsor, whichever comes first (for Phase 2: maximum up to 27 months)

Secondary Outcomes

Safety of the APX005M and Nivolumab Combination (Phase 2)

Number of participants with TEAEs are reported.

Time frame: Day 1 up to 30 days (or 100 days for SAEs and AEs with potential immunologic etiology) following the after the last dose of APX005M and/or nivolumab (from start of treatment up to 27 months)

Duration of Response (DOR) as Per RECIST 1.1(Phase 2)

Duration of Response is defined as the time from the first evidence of confirmed partial response (PR) or better by Per RECIST v1.1 to disease progression or death due to any cause; in subjects alive without progressive disease (PD), DOR was censored on the date of the last tumor assessment. PD is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: Maximum up to 25 months

Median Progression-free Survival (PFS) (Phase 2)

Progression-free Survival (PFS) in each cohort, measured from first dose to the earlier of PD (by RECIST 1.1) or death due to any cause, whichever occurs first.

Time frame: From start of treatment (Day 1) up to 27 months

6-month PFS Rate (Phase 2)

PFS rate in each cohort, measured from first dose to the earlier of PD (by RECIST 1.1) or death due to any cause, whichever occurs first.

Time frame: * Outcome Measure Time Frame From start of treatment (Day 1) to 6 months