Advanced Solid Tumor, Adult Disease, Lung Cancer
Conditions
Keywords
IL-2, ANV419, Cancer, Relapsed, Refractory, Ipilimumab
Brief summary
The purpose of this study is to test the safety and efficacy of ANV419 (single agent) and in combination with ipilimumab in patients with relapsed/refractory advanced solid tumors.
Detailed description
The purpose of this First-in-Human, open-label, dose escalation study is to assess the initial safety and efficacy profile of ANV419 intravenous infusion alone and in combination with ipilimumab in patients with advanced solid tumours. It will evaluate the safety and tolerability of ANV419 alone and in combination with ipilimumab and, the safest and best dose of ANV419 when used alone or in combination.
Interventions
DRUGANV419
ANV419 administered by intravenous (IV) infusion
DRUGIpilimumab
Ipilimumab administered by intravenous (IV) infusion
Sponsors
Anaveon AG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability of the patient or legal guardian to understand the purpose of the study, provide signed and dated informed consent from the patient prior to performing any protocol-related procedures (including Screening evaluations), and be able and willing to comply with the study procedures. * Male or female aged ≥ 18 years. * Advanced solid tumors with evidence of progressive disease as per RECIST no longer than 3 months before Informed Consent form (ICF) signature, without any subsequent curative intent treatment. * Parts A and B only: Histologically confirmed relapsed/refractory advanced solid tumor, progressing after at least one line of treatment for advanced or metastatic disease * Part C only: Previously treated advanced NSCLC without a driver mutation who have progressed after first line standard chemo-immunotherapy: Patients must have measurable disease using RECIST v1.1, A maximum of 1 line of therapy is permitted, Patients with high expression of PD-L1 which were treated with first line checkpoint inhibitor monotherapy may have received a maximum of 2 lines of therapy * Part D only: Histologically confirmed relapsed/refractory advanced solid tumors progressing after at least one line of treatment for advanced disease. Patients with NSCLC who do not meet inclusion criteria for Part C, are eligible for Part D * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. * Adequate pulmonary, cardiovascular, hematological, liver and renal function, per Investigator judgment. * All acute toxic effects, of any prior anticancer therapy (e.g., radiotherapy, chemotherapy, or surgical procedures) must have resolved to CTCAE v5.0 grade ≤1 (except alopecia \[any grade\] or fatigue \[up to grade 2 allowed\]). * Negative serum pregnancy test at screening and a negative (urine or serum) pregnancy test within 7 days prior to study day 1 in women of childbearing potential and women \<12 months after menopause. * Women 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 until 6 months after the last dose of study treatment. They must also agree to not donate eggs (ova, oocytes) during the same timeframe. * All men with childbearing potential partners 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 treatment. They must also agree to not donate sperm during the same timeframe. * Availability and willingness of patients to obtain a baseline and on treatment biopsy of the tumor. Available archived biopsies (frozen or formalin fixed) may serve as baseline specimens, in patients who have residual tumor masses which can only be accessed with significant risk
Exclusion criteria
* Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases. Definitively treated CNS metastases (e.g., radiotherapy) stable for at least 6 weeks prior to Day 1 of study drug administration are acceptable. * Participants with an active second malignancy. Patients with precancerous lesions, concomitant early stages of prostate or breast cancer not requiring active treatment (past conditions currently resolved \> 3 years prior to Screening are also acceptable), and squamous cell carcinoma of the skin not requiring systemic treatment are acceptable. * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including uncontrolled diabetes mellitus, history of relevant pulmonary disorders, (e.g., severe bronchospasm, obstructive pulmonary disease), hyperthyroidism due to thyroiditis and known autoimmune diseases or other disease with ongoing fibrosis. Stable vitiligo, autoimmune thyroiditis, and preexisting treated type 1 diabetes are acceptable and are not
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Monotherapy: Number of Dose-Limiting Toxicities (DLTs) | Day 1 to Day 14 |
| Combination: Number of Dose-Limiting Toxicities (DLTs) | Day 1 to Day 21 |
| Monotherapy: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to 12 months |
| Combination: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to 12 months |
| Monotherapy: Recommended Phase 2 Dose | Day 1 to Day 28 |
| Combination: Recommended Phase 2 Dose | Day 1 to Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) assessed by RECIST v1.1 for solid tumors | Day 1 up to 12 months |
| Plasma concentration of ANV419 in blood | Day 1 up to 12 months |
| Quality of life assessed with European Quality of Life Five Dimensions (EQ-5D-5L) | Day 1 up to 12 months |
| Quality of life assessed with European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Day 1 up to 12 months |
| Impact of ANV419 on the expression of markers of PBMC lineage in blood | Day 1 up to 12 months |
| Levels of specific anti-ANV419 antibodies in blood | Day 1 up to 12 months |
| Disease control according to RECIST v1.1 | Day 1 up to 12 months |
| Progression-free survival (PFS) according to RECIST v1.1 | Day 1 up to 12 months |
| Duration of response (DOR) according to RECIST v1.1 | Day 1 up to 12 months |
| Overall survival (OS) | Day 1 up to 12 months |
Countries
Spain, Switzerland, United Kingdom
Outcome results
None listed