Non-small Cell Lung Cancer and Metastatic Melanoma MedDRA version: 20.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864 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: APX005M
CAS Number: NA
Current Sponsor code: APX005M
Other descriptive name: APX005M
Concentration unit: mg/ml mi
Sponsors
Apexigen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Evaluate safety of the APX005M and nivolumab combination • Evaluate the 6-month progression-free survival (PFS) rate (PFSR) in each cohort/group • Evaluate the DOR and median PFS in each cohort/group by RECIST 1.1 • Determine the immune PDn of the APX005M and nivolumab combination • Determine the PK of APX005M • Assess incidence of APX005M ADA • Identify blood and/or tumor biomarkers that correlate with efficacy and/or resistance • Evaluate the ORR by immune related RECIST (iRECIST) in each cohort/group • Evaluate DOR and median PFS in each cohort/group by iRECIST;Primary end point(s): • Establish Maximum Tolerated Dose (Phase 1b) • Overall Response Rate (rate of Complete Response and Partial Response) by RECIST 1.1 in each cohort/group (Phase 2);Timepoint(s) of evaluation of this end point: The Dose-Limiting Toxicity observation period for dose escalation is the 21 days following the first administration of APX005M and nivolumab (first 3-week cycle). Subjects will be evaluated for tumor response approximately every 8 weeks following the first dose of investigational product.;Main Objective: Phase 1b: • Determine the MTD and the RP2D of APX005M when given in combination with nivolumab Phase 2: • Evaluate the ORR by RECIST 1.1 in each cohort/group | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03 • 6-month Progression-Free Survival Rate by cohort/group (Phase 2) • Duration of Response (by RECIST 1.1) by cohort/group • Progression Free Survival (by RECIST 1.1) by cohort/group • PK parameters of APX005M, including Cmax, tmax, AUC0-t, and AUC0-~ • Presence and titer of anti-APX005M antibodies • Association between potential PDn markers and PK of APX005M; association between potential predictive biomarkers and anti-tumor activity • Overall Response Rate (rate of Complete Response + Partial Response) by iRECIST in each cohort/group (Phase 2) • Duration of Response (by iRECIST) by cohort/group • Progression Free Survival (by iRECIST) by cohort/group;Timepoint(s) of evaluation of this end point: Safety and tolerability of the APX005M and nivolumab combination will be monitored on a regular basis and prior to each dose escalation. Subjects will be evaluated for tumor response approximately every 8 weeks following the first dose of investigational product. | — |
Countries
France, Spain, United States
Contacts
Public ContactMedical Monitor
Pivotal S.L.
Outcome results
None listed