Unresectable or metastatic melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: APX005M
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not know yet
CAS Number: NA
Current Sponsor code:
Sponsors
Apexigen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed unresectable or metastatic melanoma 2. Subjects with BRAF activating mutation could have received a BRAF inhibitor and/or MEK inhibitor regimen prior to study entry 3. Signed written informed consent approved by the relevant local ethics committee(s) 4. Male or female =18 years old at time of consent 5. Measurable disease by RECIST 1.1 6. ECOG performance status of 0 or 1 7. Resolution of all disease or 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 8. 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 =9 g/dL e. Serum creatinine =1.5 mg/dL f. Calculated (using the formula of local laboratory) or measured creatinine clearance =60 mL/min g. AST and ALT =2.5 x ULN h. Total bilirubin =1.5 x ULN, or direct bilirubin =ULN for subjects with total bilirubin levels >1.5 x ULN i. 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 j. aPTT =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 9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to first dose of APX005M and a negative urine pregnancy test within the 3 days prior to first dose of investigational product, or a negative serum pregnancy test within the 3 days prior to first dose of investigational product 10. Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of study treatment and 5 months after the last dose of APX005M. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and 7 months after the last dose of APX005M 11. Available archived or fresh tumor tissue sample for biomarker analysis 12. For subjects that consent to collection of tumor biopsies at study entry and before the first scheduled tumor assessment, primary or metastatic tumor that can be safely biopsied. A minimum of 12 subjects (6 subjects within each cohort) must consent to fresh core biopsies. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous exposure to any immunomodulatory agent (such as CTLA-4, PD-1/PD-L1, IDO inhibitors, interferon, etc.) 2. Second malignancy (solid or hematologic) within the past 3 years except locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast 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) a. the use of physiologic doses of corticosteroids may beapproved 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 anticancer agent, except for hormonal therapy and palliative radiation as clinically indicated unless approved by the Apexigen Medical Monitor (or designee) 7. History of allogeneic bone marrow transplantation 8. Active, known or suspected autoimmune disease 9. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 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 sensitivity or allergy to mAbs or IgG 13. 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 14. History of any thromboembolic event within 3 months prior to first dose of investigational product or active coagulopathy 15. 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, and do not 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 metastases may participate provided they are stable after treatment (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using corticosteroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability 16. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection 17. Has received
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the overall response rate (ORR) by RECIST 1.1 in immunotherapy naïve subjects with unresectable or metastatic melanoma in each dosing schedule; Secondary Objective: Evaluate the safety of APX005M in immunotherapy naïve subjects with unresectable or metastatic melanoma Evaluate ORR by modified RECIST 1.1 for immune-based therapeutics (iRECIST) in each dosing schedule Evaluate median duration of response (DOR) in each dosing schedule Evaluate PFS (by RECIST 1.1 and iRECIST) in each dosing schedule Evaluate the association between potential predictive biomarkers and antitumor activity and/or resistance Determine the presence and titer of anti-APX005M antibodies (ADA) ;Primary end point(s): Overall response rate (ORR) (rate of Complete response (CR) and Partial response (PR)) by RECIST 1.1 in each dosing schedule;Timepoint(s) of evaluation of this end point: Every 8 weeks (+/- 1 week) following the first dose of APX005M. Tumor assessments will follow RECIST 1.1 guidelines. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03 Changes from baseline of vital signs and clinical laboratory results during and following investigational product administration ORR (rate of CR and PR) by iRECIST in each dosing schedule DOR (by RECIST 1.1) by dosing schedule, defined as the time from the first evidence of confirmed PR or better to disease progression or death due to any cause ;Timepoint(s) of evaluation of this end point: Each study visit following first dose of APX005M-010, through 30 days after receiving the last dose of APX005M-010 | — |
Countries
Spain
Contacts
Public ContactMedical Monitor
Pivotal S.L.
Outcome results
None listed