Unresectable or Metastatic Cutaneous Melanoma with prior Anti PD 1/Anti-PD-L1 Antibody Treatment MedDRA version: 21.1 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Anaveon AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Must provide written informed consent for the study; - Must be able to comply with the Protocol as judged by the Investigator; - Are 18 years of age and older on day of signing informed consent; - Have histologically confirmed Stage 3 (unresectable) or Stage 4 (metastatic) CM, as per the American Joint Committee on Cancer staging system, eighth edition; - Have experienced disease progression during treatment with anti-PD-1/anti-PD-L1 antibody as a treatment regimen prior to study enrollment, or disease progression within 6 months of adjuvant anti-PD-1 antibody. In the metastatic setting, patients must have received 1 line of immunotherapy (regimen containing anti-PD-1, anti-PD-L1, and/or CTLA 4) and have experienced at least a stable disease response for at least 6 weeks; - Patients must have confirmed results of BRAF mutation status. Patients with BRAF mutation must have received treatment with a BRAF and MEK inhibitor before study enrollment; - Have measurable disease based on RECIST; - Have a performance status of 0 or 1 on the ECOG Performance Status; - Have adequate organ functions as defined in protocol; - Female patients of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative (urine or serum) pregnancy test within 72 hours prior to study Day 1; - Female patients who are not postmenopausal, and who have not undergone surgical sterilization, must agree to use highly effective methods of contraception during the treatment period and for 6 months after the last dose of study drug. They must also agree not to donate eggs (ova, oocytes) during the same timeframe; - Male patients with partners of childbearing potential must agree to use highly effective methods of contraception and barrier contraception (condom) during the treatment period and for 6 months after the last dose of study drug. They must also agree not to donate sperm during the same timeframe. 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 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: - Have received investigational agent within 4 weeks or an interval of 5 half-lives of the respective investigational agent prior to study Day 1, whichever is longer, with the exclusion of an anti PD 1/anti PD-L1 antibody given as either a single agent or non-CTLA-4 antibody containing combination; - Have a known hypersensitivity to ANV419 or to any of the excipients, such as sucrose, histidine or polysorbate 80. For combination arms only: Have hypersensitivity to pembrolizumab or ipilimumab or any of their excipients; - For combination arms only: Have previously discontinued pembrolizumab or ipilimumab due to unacceptable drug-related toxicity; - Have a LDH level of >=2 × upper limit of normal; - Have not recovered from adverse events (AEs) resulting from prior immunotherapies. - Have not recovered from toxicities due to a previously administered chemotherapy, targeted small molecule therapy, or radiation therapy; - Have been diagnosed with uveal/ocular or mucosal melanoma; - Have a known additional malignancy (including all in-situ carcinoma) that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy or in situ cervical cancer or patients who completed cancer-directed therapy >=2 years prior to enrollment and have evidence of stable disease or no evidence of disease; - Have active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study Day 1, and any neurologic symptoms have returned to baseline or have been stable for at least 7 days), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study drug. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability; - Have a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days prior to study Day 1; - Are receiving systemic steroid >10 mg of prednisone daily or equivalent or any other immunosuppressive medication at any dose level. Local steroid therapies (eg, otic, ophthalmic, intra-articular, or inhaled medications) are acceptable. - Have an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment. - Have a known history of, or any evidence of active, non-infectious pneumonitis; - Have active (measurable) and uncontrolled (unresponsive to current therapy) infectious disease (bacterial, fungal, viral, protozoic); - Have a history of an acute coronary event (eg, myocardial infarction) within 3 months prior to study Day 1, uncontrolled and symptomatic coronary artery disease or congestive heart failure New York Heart Association Class III/IV; - Have an average QTcF interval >470 msec at Screening; - Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or it is not in the best interest of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective during Monotherapy Dose Expansion Phase is to evaluate the efficacy of ANV419 as monotherapy following at least 1 line of standard of care immunotherapy. Primary objective during Combination Dose Finding Phase is to evaluate the safety and tolerability and determine the RP2D of ANV419 in combination with pembrolizumab or with ipilimumab. Primary objective during Combination Dose Expansion Phase is to evaluate the efficacy of ANV419 in combination with pembrolizumab or ipilimumab following at least 1 line of standard of care immunotherapy.;Secondary Objective: Monotherapy Dose Expansion: characterize the tumor response according to modified RECIST v1.1 criteria for immune-based therapeutics; expand evaluation of efficacy of ANV419; evaluate the safety of ANV419; explore immunogenicity after exposure to ANV419 Combination Dose Finding: evaluate PK and PD of ANV419 in combination with pembrolizumab [pembro] or ipilimumab [ipi]; explore immunogenicity after exposure to ANV419 in combination with pembro or ipi; evaluate the efficacy of ANV419 in combination with pembro or ipi; evaluate clinical benefit in QoL after exposure to ANV419 in combination with pembro or ipi Combination Dose Expansion: expand evaluation of efficacy of ANV419 in combination with pembro or ipi; evaluate the safety of ANV419 in combination with pembro or with ipi; evaluate clinical benefit in QoL after exposure to ANV419 in combination with pembro or ipi; explore immunogenicity after exposure to ANV419 in combination with pembro or ipi;Primary end point(s): Monotherapy Dose Expansion Phase: ORR (CR + PR); as defined by RECIST Combination Dose Finding Phase: Incidence, frequency, and severity of AEs including the following: SAEs, TEAEs, DLTs, AESIs, irAEs, AEs leading to discontinuation of the study, and Changes in baseline in laboratory parameters, vital signs, ECGs, and physical examinations. Combination Dose Expansion Phase: ORR (CR + PR), as defined by RECIS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Monotherapy Dose Expansion Phase: - Tumor response in terms of objective response rate (ORR: CR + PR) assessed by RECIST - DOR (per RECIST) and iDOR (per iRECIST[1]) measured from first response until disease progression; DCR (DCR = CR + PR + SD), iDCR (iDCR = iCR + iPR + iSD), PFS, iPFS, and OS; Median TTR; and Median iTTR - Incidence, frequency, and severity of AEs including SAEs; irAEs; AESIs; AEs leading to discontinuation of the study; and changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination - Incidence of immunogenicity as indicated by ADA Combination Dose Finding Phase: - PK endpoints in serum: CL of ANV419, Vss of ANV419, AUC of ANV419, and Cmax of ANV419 - PD endpoints in peripheral blood: including, but not limited to, CD3, CD4, CD8, CD56, CD16, CD25, FoxP3, CD279, and CD366 - Incidence of immunogenicity as indicated by ADA - ORR ( CR + PR), as defined by RECIST - Change in QoL at baseline and every 12 weeks while receiving ANV419 via QoL evaluations: EQ-5D-5L, and QLQ-C30 Combination Dose Expansion Phase: - DOR (per RECIST) and iDOR (per iRECIST[1]) measured from first response until disease progression - DCR (DCR = CR + PR + SD), iDCR (iDCR = iCR + iPR + iSD), PFS, iPFS, and OS - Median TTR - Median iTTR - Incidence, frequency, and severity of AEs including the following: SAEs, irAEs, AESIs, AEs leading to discontinuation of the study, and Changes in baseline in laboratory parameters, vital signs, ECGs, and physical examination - Change in QoL at baseline and every 12 weeks while receiving ANV419 via QoL evaluations: EQ-5D-5L, QLQ-C30 - Incidence of immunogenicity as indicated by ADA. | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactSilvio Costanzo
Anaveon AG
Outcome results
None listed