A Study of ANV419 Alone or in Combination With Approved Treatments in Patients With Multiple Myeloma (OMNIA-2)

• ClinicalTrials.gov Identifier: NCT05641324
• Recruitment Status: Terminated
• First Posted: December 7, 2022
• Last Update Posted: February 12, 2024
• Sponsor: Anaveon AG
• Information provided by (Responsible Party): Anaveon AG

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety and tolerability of ANV419 monotherapy followed by ANV419 in combination with lenalidomide plus low-dose dexamethasone or ANV419 in combination with daratumumab.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Relapsed Cancer; Refractory Multiple Myeloma; Adult Disease; Hematologic Diseases	Drug: ANV419; Drug: Lenalidomide with low-dose dexamethasone; Drug: Daratumumab	Phase 1

Detailed Description:

The purpose of this multi-site, open-label, Phase 1 adaptive design study is to evaluate the safety, tolerability and preliminary efficacy of ANV419 as a monotherapy followed by ANV419 in combination with lenalidomide plus low-dose dexamethasone or ANV419 in combination with daratumumab in patients aged 18 years or older with with relapsed or refractory Multiple Myeloma.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of ANV419 as Monotherapy, and ANV419 in Combination With Daratumumab or With Lenalidomide Plus Low-Dose Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma (OMNIA-2)
• Actual Study Start Date: February 10, 2023
• Actual Primary Completion Date: July 12, 2023
• Actual Study Completion Date: July 12, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: ANV419 single agent, dose 1, Q2W	Drug: ANV419; ANV419 administered by intravenous (IV) infusion
Experimental: ANV419 single agent, dose 2, Q2W	Drug: ANV419; ANV419 administered by intravenous (IV) infusion
Experimental: ANV419 Q2W + Lenalidomide plus low-dose dexamethasone	Drug: ANV419; ANV419 administered by intravenous (IV) infusion; Drug: Lenalidomide with low-dose dexamethasone; Lenalidomide and dexamethasone administered orally
Experimental: ANV419 Q2W + Daratumumab	Drug: ANV419; ANV419 administered by intravenous (IV) infusion; Drug: Daratumumab; Daratumumab administered by subcutaneous injection

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) with ANV419 monotherapy [ Time Frame: Day 1 up to 12 months ]
2. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) with ANV419 in combination with lenalidomide plus low-dose dexamethasone [ Time Frame: Day 1 up to 12 months ]
3. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) with ANV419 in combination with daratumumab [ Time Frame: Day 1 up to 12 months ]

Secondary Outcome Measures :

1. Serum concentration of ANV419 in blood [ Time Frame: Day 1 up to 12 months ]
2. Impact of ANV419 on the expression of markers of PBMC lineage in blood [ Time Frame: Day 1 up to 12 months ]
3. Levels of specific anti-ANV419 antibodies in blood [ Time Frame: Day 1 up to 12 months ]
4. Objective Response Rate (ORR) as defined by IMWG response criteria, with ANV419 monotherapy [ Time Frame: Day 1 up to 12 months ]
5. Objective Response Rate (ORR) as defined by IMWG response criteria, with ANV419 in combination with lenalidomide plus low-dose dexamethasone [ Time Frame: Day 1 up to 12 months ]
6. Objective Response Rate (ORR) as defined by IMWG response criteria, with ANV419 in combination with daratumumab [ Time Frame: Day 1 up to 12 months ]
7. Quality of life assessed with European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) [ Time Frame: Day 1 up to 12 months ]
8. 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 ]
9. Progression-free survival (PFS) according to IMWG response criteria [ Time Frame: Day 1 up to 12 months ]
10. Duration of Response (DOR) according to IMWG response criteria [ Time Frame: Day 1 up to 12 months ]
11. Clinical Benefit Rate (CBR) according to IMWG response criteria [ 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:

• 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 on the day of signing informed consent
• Have been diagnosed with symptomatic MM per CRAB (calcium elevation, renal dysfunction, anemia, bone disease) criteria;
• Have had evidence of a response (defined as partial response [PR] or better according to IMWG response criteria [Appendix C]) during previous treatment;
• Have undergone treatment with ASCT or have progressed from at least 2 other prior treatment lines (including an immunomodulatory imide drug and/or daratumumab);
• Have relapsed on, or been refractory or intolerant to, the last treatment line, and have measurable disease evaluated by monoclonal proteins (M-proteins) and/or free light chains according to IMWG response criteria (Appendix C). Non-secretory MM must have measurable, active lesions by positron emission tomography;
• Have a performance status of 0 to 2 on the ECOG Performance Status;
• Have adequate organ functions;
• Willing to undergo bone marrow biopsies if determined clinically feasible based on the Investigator's assessment;
• Are eligible for treatment with daratumumab;
• Are eligible for treatment or re-treatment with lenalidomide (as per the European Medicines Agency labeling criteria);
• Are eligible for prophylaxis for thromboembolism per IMWG response criteria;
• Female patients of childbearing potential must have a negative serum pregnancy test at screening and a negative (urine or serum) pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible;
• 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; and
• 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.

Exclusion Criteria:

• Have received an investigational agent (including investigational device) <4 weeks or 5 half-lives prior to study Cycle 1 Day 1, whichever is longer;
• Have hypersensitivity to any components of ANV419 (IL-2, anti-IL-2 mAb) or its formulation (L-histidine, L-histidine HCl, sucrose, polysorbate 80, water; see Appendix D);
• Have hypersensitivity to lenalidomide, dexamethasone, daratumumab, or any of their excipients;
• Have received daratumumab <3 months prior to the signing of informed consent;
• Have received any drugs that may be active for MM <3 weeks prior to the signing of informed consent;
• Have received high-dose corticosteroids (≥1 mg/kg) ≤3 weeks prior to the signing of informed consent;
• Have received radiotherapy ≤1 month prior to the signing of informed consent;
• Have had an autologous hematopoietic cell transplant (HCT) within the last 6 months;
• Have had a previous allogeneic HCT;
• Have had major surgery <4 weeks prior to the signing of informed consent or anticipate the need for major surgery during treatment; Note: Major surgery is defined as any surgery requiring entrance into a body cavity (eg, chest, abdomen, or brain), organ removal, normal anatomy alteration, or joint replacement. Minor surgery is defined as any surgery in which skin, mucosa, or connective tissue sections are altered (eg, biopsy, cataract, endoscopic procedures, etc).
• Have clinical signs of meningeal involvement of MM;

• Have a history of a past or current malignancy prior to screening, except for:

  1. Cervical carcinoma of Stage 1B or less;
  2. Non-invasive basal cell or squamous cell skin carcinoma requiring treatment; or
  3. Current or past malignancy with a complete response for <3 years at screening.
• Have plasma cell leukemia defined as a plasma cell count >2000/mm3;
• Have known amyloidosis;
• Have sensory and/or motor neuropathy ≥Grade 3 per NCI CTCAE version 5.0 at screening;
• Have active (measurable) and/or uncontrolled (unresponsive to current therapy) infectious disease (bacterial, fungal, viral, or protozoic);
• Have evidence of uncontrolled (unresponsive to current therapy), concomitant disease including, but not limited to, uncontrolled diabetes mellitus (pre-existing diabetes mellitus type 1 is acceptable), chronic obstructive pulmonary diseases Grade 3 (per NCI CTCAE version 5.0) or higher, asthma, bronchospasm, obstructive pulmonary disease, hematological diseases except MM, renal impairment (except when related to MM), hyperthyroidism due to thyroiditis, known autoimmune disease, or disease with ongoing fibrosis;
• Have clinically significant (defined as a disease that requires intervention) cardiovascular disease including, but not limited to, acute myocardial infarction and/or transient ischemic attack <6 months prior to screening, unstable angina, congestive heart failure (New York Heart Association Class II or higher), or arrhythmia requiring therapy;
• Have an average QTcF interval >480 msec at screening;
• Have active, untreated, immune-related endocrinopathy untreatable with hormone replacement or prior immune-related toxicities (eg, colitis, neuropathy) >Grade 3 (per NCI CTCAE version 5.0) after treatment with immunostimulatory drugs that have not been resolved;
• Have evidence of severe hepatic impairment (equivalent to Child-Pugh Class C [for liver cirrhosis] or a MELD [Model for End-Stage Liver Disease] score of 10 or higher for hepatic impairment not limited to cirrhosis]);
• Have a history or current evidence of any condition, therapy, or laboratory abnormality that might significantly 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 patient to participate in the study, in the opinion of the treating Investigator;
• Have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study;
• Are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, from screening through 6 months after the last dose of study drug;

• Are known to be human immunodeficiency virus (HIV) positive (or tests positive for HIV 1 or 2 at screening), unless the following criteria are met:

  1. CD4+ lymphocyte count >350 µL;
  2. Had no history of AIDS (acquired immunodeficiency syndrome)-defining opportunistic infections within the past 12 months;
  3. Have been on established anti-retroviral therapy for at least 4 weeks; and
  4. Have an HIV viral load of <400 copies/mL prior to study Day 1. Note: Patients on strong cytochrome P450 (CYP)3A4 inhibitors or strong CYP3A4 inducers must be switched to an alternate effective anti-retroviral therapy regimen prior to study treatment or are excluded if regimen prior to study Day 1 cannot be altered.
• Have uncontrolled hepatitis B infection or hepatitis C infection; Note: Patients with hepatitis B (positive hepatitis B surface antigen) who have controlled infection (serum hepatitis B virus DNA by PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of hepatitis B virus DNA. Note: Patients with hepatitis C (positive hepatitis C virus antibody) who have controlled infection (undetectable hepatitis C virus RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C virus therapy) are permitted.
• Have received a live vaccine within 30 days of study Day 1. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed

Contacts and Locations

Locations

Denmark

Vejle Hospital

Vejle, Denmark

France

Institut Paoli-Calmettes

Marseille, France

CHU de Nantes - Hôtel-Dieu

Nantes, France

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, France

Germany

Universitätsklinikum Jena

Jena, Germany, 07747

Spain

Hospital Clinic Barcelona

Barcelona, Spain

Hospital Universitario La Princesa

Madrid, Spain, 28006

Hospital General Universitario Morales Meseguer

Murcia, Spain

Hospital Clinico Universitario de Salamanca

Salamanca, Spain

Switzerland

Inselspital, Universitätsspital Bern

Bern, Switzerland

Kantonsspital St. Gallen

Saint Gallen, Switzerland

Sponsors and Collaborators

Anaveon AG

Investigators

• Study Director: Eduard Gasal, MD; Anaveon AG

More Information

• Responsible Party: Anaveon AG
• ClinicalTrials.gov Identifier: NCT05641324
• Other Study ID Numbers: ANV419-102
• First Posted: December 7, 2022
• Last Update Posted: February 12, 2024
• Last Verified: February 2024

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; Multiple Myeloma; OMNIA

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Lenalidomide; Daratumumab; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors