A Study to Evaluate Sotigalimab (APX005M) in Subjects With Unresectable or Metastatic Melanoma
Condition: Unresectable Melanoma; Metastatic Melanoma; Cancer; Cancer of Skin; Melanoma; Melanoma (Skin)
MeSH terms: Melanoma; Skin Neoplasms
Intervention: sotigalimab
Intervention description: Sotigalimab is a CD40 agonistic monoclonal antibody
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Enrolled participants will be alternately assigned to one of the following 2 cohorts (groups) as long as the cohorts are open:
Cohort 1: APX005M administered IV at 0.3 mg/kg every 3 weeks (21-day cycle) Cohort 2: APX005M administered IV at 0.3 mg/kg every 2 weeks (14-day cycle) Enrolled participants assigned to Cohorts 1 or 2 that do not receive sotigalimab or are not evaluable for tumor response will be replaced in that cohort before assigning new participants to the other cohort.
Cohort 3: Participants who have failed any number of prior lines of therapy, sotigalimab administered IV at 0.3 mg/kg in combination with radiation therapy every 2 weeks (14 day cycle) up to 16 weeks followed by sotigalimab administered IV at 0.3 mg/kg every 2 weeks (14-day cycle).
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CD40; Immunotherapy; APX005M; sotigalimab

Summary:

      This is a multicenter, open label, Phase 2 study, with 3 parallel cohorts. The aim of the
      study is to evaluate the efficacy of sotigalimab (APX005M) administered at 2 different
      schedules to adult participants with unresectable or metastatic melanoma. Participants who
      have not received prior immunotherapy will be alternately assigned to 1 of 2 cohorts with
      different sotigalimab administration schedules as long as both are open for enrollment.
      Participants who have failed any number of prior lines of therapy will be assigned to a 3rd
      cohort of sotigalimab in combination with radiation therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically confirmed unresectable or metastatic melanoma

          2. Subjects with BRAF activating mutation must 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

             a. For Cohort 3 only, subjects must have at least 3 measurable target lesions

          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 prior to first dose of investigational
             therapy(ies):

               1. WBC ≥2 x 109/L in absence of growth factor support

               2. ANC ≥1.0 x 109/L in absence of growth factor support

               3. Platelet count ≥100 x 109/L

               4. Hemoglobin ≥9 g/dL

               5. Serum creatinine ≤1.5 mg/dL

               6. Calculated (using the formula of local laboratory) or creatinine clearance ≥60
                  mL/min

               7. AST and ALT ≤2.5 x ULN

               8. Total bilirubin ≤1.5 x ULN, or direct bilirubin ≤ULN with total bilirubin levels
                  >1.5 x ULN

               9. INR or PT ≤1.5 x ULN unless receiving anticoag therapy PT or PTT is within
                  therap, range

              10. aPTT ≤1.5 x ULN unless receiving anticoag therapy PT or PTT is within therap
                  range

          9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
             within the 7 days prior to first dose of investigational therapy(ies) and a negative
             urine pregnancy test within the 3 days prior to first dose of investigational
             therapy(ies), or a negative serum pregnancy test within the 3 days prior to first dose
             of investigational therapy(ies)

         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
             investigational therapy(ies). 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 investigational therapy(ies)

         11. Available archived or fresh tumor tissue sample for biomarker analysis. Cohort 3, only
             available archived tissue is required.

         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. Up to 18 subjects (6 subjects within each cohort) should consent to fresh
             core biopsies.

        Exclusion Criteria:

          1. Prior Therapy:

               1. Cohorts 1 and 2 only: Previous exposure to any immunomodulatory agent (such as
                  CTLA-4, PD-1/PD-L1, IDO inhibitors, interferon, CD40 agonist etc.).

               2. Cohort 3 only: Prior therapy with a CD40 agonist. Any number of prior lines of
                  therapy are eligible. A minimum washout period of 21 days from last line of
                  therapy until investigational therapy(ies) administration should be observed.

          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 therapy(ies)

          4. Use of systemic corticosteroids or other systemic immunosuppressive drugs within 28
             days prior to first dose of investigational therapy(ies) (except inhaled
             corticosteroids)

             a. The use of physiologic doses of corticosteroids may be approved /w consultation
             Medical Monitor (or designee)

          5. Major surgery within 4 weeks prior to first dose of sotigalimab

          6. Concurrent treatment with any anticancer agent and palliative radiation, unless
             approved by MM (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 1 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
             therapy(ies)

         14. History of any thromboembolic event within 3 months prior to first dose of
             investigational therapy(ies) 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 a live (attenuated) vaccine within 30 days prior to the first dose of
             investigational therapy(ies). Seasonal flu vaccines that do not contain live virus and
             COVID 19 vaccines are permitted (see Section 3.2.3.4)

         18. Has participated in another clinical trial of an investigational drug (or a medical
             device) within 30 days of study enrollment

         19. Pregnant, breastfeeding, or unwilling to practice birth control during participation
             in the study

         20. Any clinically significant psychiatric, social, or medical condition that, in the
             opinion of the Investigator, could increase subject's risk, interfere with protocol
             adherence, or affect a subject's ability to give informed consent.