A Study to Evaluate the Safety and Efficacy of the CD40 Agonistic Antibody APX005M Administered in Combination with Nivolumab in Subjects with Non-small Cell Lung Cancer and Subjects with Metastatic Melanoma

Phase 1

Conditions: on-small Cell Lung Cancer and Metastatic Melanoma
MedDRA version: 20.0Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003866-14-FR

Lead Sponsor: Apexigen, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 174

Inclusion Criteria

Phase Specific Criteria
Phase 1b: Subjects that meet eligibility criteria for Phase 2 Cohorts 1 or 2 and all of the general eligibility criteria
Phase 2 Cohort 1 (inNSCLC): Histologically or cytologically confirmed, immunotherapy naïve, metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment. Subjects may be treatment naïve or could have received one prior platinum-based chemotherapy for non-small cell lung cancer for any indication (adjuvant, part of combined modality therapy or for metastatic disease) within the past 3 years. Subjects with no or unknown activating mutation (e.g., EGFR, ALK, ROS) are eligible for this study. Subjects with a documented activating mutation (e.g., EGFR, ALK, ROS) amenable to tyrosine kinase inhibitor therapy, must also have received the appropriate therapy and progressed.
Phase 2 Cohort 2 (PD1-MM): Subjects with histologically or cytologically confirmed unresectable or metastatic melanoma that had confirmed progressive disease during treatment with anti-PD-1/PD-L1 therapy. Subjects with BRAF wild type or unknown status must have received only anti-PD-1/PD-L1 therapy. 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. Subjects with ocular melanoma are excluded.
Phase 2 Cohort 3 (PD1-NSCLC): Subjects with histologically or cytologically confirmed, metastatic or locally advanced NSCLC not amenable to curative treatment. Subjects must have disease progression on an immediately preceding PD-1/PD-L1 containing regimen. Subjects could have received no more than one platinum containing regimen, or if subjects have a documented activating mutation (e.g. EGFR, ALK, ROS) amenable to tyrosine kinase inhibitor therapy, must also have received the appropriate therapy and progressed before the PD-1/PD-L1 containing regimen. Based on response to previous PD-1/PD-L1 containing regimen, subjects will be enrolled in one of the following groups:
•Group A: Subjects with best response of progressive disease or with stable disease < 16 weeks
•Group B: Subjects with tumor response or with stable disease = 16 weeks
General Inclusion Criteria:
1.Subjects willing and able to provide written informed consent for this study
2.Male or female =18 years old at time of consent
3.Measurable disease by RECIST 1.1
4.ECOG performance status of 0 or 1
5.Resolution of prior treatment-related toxicities to Grade 1, with the exception of alopecia, Grade 2 neuropathy and laboratory abnormalities (parameters below apply). If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention
6.Adequate organ function within 14 days of first dose of investigational product:
a.WBC =2 x 109/L in absence of growth factor support
b.ANC =1.0 x 109/L in absence of growth factor support
c.Platelet count =100 x 109/L
d.Hemoglobin =8 g/dL
e.Serum creatinine =1.5 mg/dL AND creatinine clearance =60 mL/min (calculated [using the formula of local laboratory] or measured)
f.AST and ALT =2.5 x ULN
g.Total bilirubin =1.5 x ULN, or direct bilirubin =ULN for subjects with total bilirubin levels >1.5 x ULN
h.INR or PT =1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
i.aPTT =1.5 x ULN unless subject is receiving anticoagulant therapy as long as P

Exclusion Criteria

General Exclusion Criteria:
1.Previous exposure to any immunomodulatory agents (e.g., anti- CD40, CTLA-4, PD-1/ PD-L1, IDO inhibitors) with the following exceptions:
a.For Cohort 2 (unresectable or metastatic melanoma):
i. All subjects must have confirmed disease progression while on treatment with anti-PD-1/PD-L1 therapy
ii.Subjects could have received anti-CTLA-4 therapy provided they did not have disease progression while on therapy and they discontinue treatment with anti-CTLA-4 therapy at least 3 months prior to first dose of investigational product
b.For Cohort 3 (metastatic or locally advanced NSCLC):
i.All subjects must have disease progression while on treatment with anti-PD-1/PD-L1 therapy
2.Second malignancy (solid or hematologic) within the past 3 years except:
a.Adequately treated basal cell or squamous cell skin cancer, or
b.Carcinoma in situ of the cervix, or
c.Prostate cancer Gleason score < 6 with undetectable prostate specific antigen (PSA) over 12 months, or
d.Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins), or
e.Treated medullary or papillary thyroid cancer
3.Active, known, clinically serious infections (= Grade 2 according to NCI-CTCAE v4.03) within the 14 days prior to first dose of investigational product
4.Use of systemic corticosteroids or other systemic immunosuppressive drugs within the 28 days prior to first dose of investigational product (except inhaled corticosteroids); the use of physiologic doses of corticosteroids may be approved after consultation with the Apexigen Medical Monitor (or designee)
5.Major surgery within 4 weeks of first dose of investigational product
6.Concurrent treatment with any anti-cancer agent, except for hormonal therapy and palliative radiation as clinically indicated unless approved by the Medical Monitor
7.History of allogeneic bone marrow transplantation
8.Uncontrolled diabetes or hypertension
9.Active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
10.History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis
11.History of interstitial lung disease
12.History of life-threatening toxicity related to prior anti-PD-1/PD-L1 treatment for subjects with metastatic melanoma except those that are unlikely to re-occur with standard countermeasures (e.g. hormone replacement after adrenal crisis)
13.History of sensitivity or allergy to mAbs or IgG
14.Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to the first dose of investigational product
15.History of any thromboembolic event within 3 months prior to first dose of investigational product or an active coagulopathy
16.Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with untreated brain metastases = 3mm that are asymptomatic, do not have significant edema, cause shift, require steroids or anti-seizure medications are eligible after discussion with the Medical Monitor. Lesions of any size in posterior fossa are excluded. Subjects with previously treated brain met

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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