A Study Evaluating Safety and Therapeutic Activity of ANV419 in Patients With Advanced Cancer and Multiple Myeloma. (ANV419-001)

• ClinicalTrials.gov Identifier: NCT04855929
• Recruitment Status: Recruiting
• First Posted: April 22, 2021
• Last Update Posted: February 4, 2022
• Sponsor: Anaveon AG
• Information provided by (Responsible Party): Anaveon AG

Study Description

Brief Summary:

The purpose of this study is to test the safety and efficacy of ANV419 (single agent and combination therapy) in patients with relapsed/refractory advanced solid tumors and multiple myeloma.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Adult Disease; Multiple Myeloma	Drug: ANV419; Drug: CPI or Immunostimulatory agent	Phase 1; Phase 2

Detailed Description:

The purpose of this First-in-Human, open-label, dose escalation and expansion study is to assess the initial safety and efficacy profile of ANV419 intravenous infusion in patients with advanced solid tumours and multiple myeloma. Phase 1 will evaluate the safety and tolerability of ANV419 alone and to determine a suitable dose for Phase 2 development. Phase 2 will evaluate the preliminary efficacy and, the safest and best dose of ANV419 when used alone or together with established cancer treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ANV419 Single Agent (Parts A-C) or Combination (Part D) First in Human Study Phase 1/2: Open-label, Dose Escalation and Expansion Study in Patients With Relapsed/Refractory Advanced Solid Tumors and Multiple Myeloma.
• Actual Study Start Date: May 25, 2021
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: ANV419 single agent, Q2W	Drug: ANV419; ANV419 administered by intravenous (IV) infusion
Experimental: ANV419 in combination with CPI or Immunostimulatory agent, Q2W	Drug: ANV419; ANV419 administered by intravenous (IV) infusion; Drug: CPI or Immunostimulatory agent; CPI or other immunostimulatory administred per treatment modalities

Outcome Measures

Primary Outcome Measures :

1. Phase I: Number of Dose-Limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 14 ]
2. Phase I: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to 12 months ]
3. Phase I: Recommended Phase 2 Dose [ Time Frame: Day 1 to Day 28 ]
4. Phase II: Objective Response Rate (ORR) assessed by RECIST v1.1 or (ORR) according to IMWG2016 [ Time Frame: Day 1 up to 12 months ]

Secondary Outcome Measures :

1. Phase I: Objective response rate (ORR) assessed by RECIST v1.1 and iRECIST for solid tumors and IMWG2016 for multiple myeloma [ Time Frame: Day 1 up to 12 months ]
2. Phase II: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Day 1 up to 12 months ]
3. Phase II: Objective Response Rate (ORR) assessed by iRECIST or (ORR) according to IMWG2016 [ Time Frame: Day 1 up to 12 months ]
4. Plasma concentration of ANV419 in blood [ Time Frame: Day 1 up to 12 months ]
5. Impact of ANV419 on the expression of markers of PBMC lineage in blood [ Time Frame: Day 1 up to 12 months ]
6. Levels of specific anti-ANV419 antibodies in blood [ Time Frame: Day 1 up to 12 months ]
7. Disease control according to RECIST v1.1 and iRECIST or IMWG2016 [ Time Frame: Day 1 up to 12 months ]
8. Progression-free survival (PFS) according to RECIST v1.1 and iRECIST or IMWG2016 [ Time Frame: Day 1 up to 12 months ]
9. Duration of response (DOR) according to RECIST v1.1 and iRECIST or IMWG2016 [ Time Frame: Day 1 up to 12 months ]
10. Overall survival (OS) [ Time Frame: Day 1 up to 12 months ]
11. Quality of life assessed with European Quality of Life Five Dimensions (EQ-5D-5L) [ Time Frame: Day 1 up to 12 months ]
12. Quality of life assessed with European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Day 1 up to 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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, or for multiple myeloma, progressing during or after at least three lines of treatment including an -IMiD, a proteasome inhibitor and a aCD38 agent.
• Patients with multiple myeloma (MM) must have measurable disease (non-secretory MM must have measurable active lesions in PET) and have had evidence of a previous response (PR or better) to lenalidomide or daratumumab according to IMWG2016.
• Parts C and D only: Histologically confirmed solid tumors, relapsed post or were refractory to at least one line of treatment for advanced disease. BRAF mutant melanoma must have progressed to BRAF + MEK inhibitor.
• Parts C and D only: Measurable disease as per RECIST v1.1 or IMWG 2016.
• No additional established line of on-label treatment is available or there is a contraindication for the indicated labelled therapies as deemed by the Investigator.
• 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 within 7 days prior to study treatment 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:

• 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 exclusion criteria.
• Significant cardiovascular/cerebrovascular disease, including myocardial infarction or transient ischemic attack (TIA) within 6 months prior to Day 1 of study drug administration.
• Active or uncontrolled infections requiring systemic antibiotics within one week (7 days) preceding Day 1 of treatment
• Hemoglobin (Hb) <9 g/dL, transfusion of red blood cells allowed to reach threshold target.
• Neutrophils <1500 /mm3.
• Platelets <100000/mm3.
• Liver: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5xULN.
• Total bilirubin > upper limit of normal (ULN) (in documented Gilbert's syndrome, direct bilirubin > ULN) however, if due to liver metastasis, AST or ALT >5x ULN.
• International normalized ratio (INR) >1.5xULN.
• Serum creatinine > ULN or estimated creatinine clearance < 50 mL/min using the Cockcroft-Gault formula.
• Known replicating human immunodeficiency virus (HIV) or known active (replicative) hepatitis B virus or hepatitis C virus infection. Patients with treated non-replicative disease are acceptable.
• Positivity for coronavirus disease 2019 (COVID-19) by naso-pharyngeal swab test. Known serologic conversion is not an exclusion criterion.
• Evidence of hepatic cirrhosis with Child-Pugh score C.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding > Grade 2 that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
• Major surgery or significant traumatic injury <28 days prior to the first ANV419 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment.
• Severe altered mental status.
• Pregnant or breastfeeding women.
• Known hypersensitivity to any of the components of ANV419 or its formulation.
• Concurrent therapy with any other investigational drug within one month prior to Day 1 of study drug administration.
• Active untreated immune-related endocrinopathies untreatable with replacement. Prior immune related toxicities > Grade 3 after treatment with immunostimulatory drugs (e.g., colitis, neuropathy) that have not completely resolved.
• Chronic treatment with systemic immunosuppressive medications above 10 mg/day prednisolone equivalent for any reason.

Contacts and Locations

Contacts

Contact: Christoph Bucher, Dr; 0041768243366; anv419-001clinicaltrial@anaveon.com

Contact: Andreas Katopodis; 0041797308717; anv419-001clinicaltrial@anaveon.com

Locations

Spain

Hospital Vall d'Hebrón; Recruiting

Barcelona, Spain

START Madrid, Hospital Universitario HM Sanchinarro; Recruiting

Madrid, Spain

Switzerland

University Hospital Basel; Recruiting

Basel, Switzerland

Cantonal Hospital St.Gallen; Recruiting

Saint-Gall, Switzerland

United Kingdom

Royal Marsden Hospital; Recruiting

London, United Kingdom

Sponsors and Collaborators

Anaveon AG

Investigators

• Study Director: Christoph Bucher; Anaveon AG

More Information

• Responsible Party: Anaveon AG
• ClinicalTrials.gov Identifier: NCT04855929
• Other Study ID Numbers: ANV419-001
• First Posted: April 22, 2021
• Last Update Posted: February 4, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anaveon AG:

IL-2; ANV419; Cancer; Relapsed; Refractory; Myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases