A Study of ANV419 Alone or in Combination With Approved Treatment in Patients With Cutaneous Melanoma (OMNIA-1).

Sponsor

Anaveon AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05578872

Collaborator

(none)

130

Enrollment

Locations

Arms

23.5

Anticipated Duration (Months)

16.3

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ANV419 monotherapy or the combination of ANV419 with anti-PD1 antibody or with anti-CTLA4 antibody in adult participants with advanced (unresectable or metastatic) cutaneous melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin) Cutaneous Melanoma Adult Disease Advanced Solid Tumor Metastatic Melanoma	Drug: ANV419 Drug: Pembrolizumab Drug: Ipilimumab	Phase 1/Phase 2

Detailed Description

The purpose of this multi-site, open-label, randomized, parallel arm, Phase 1/2 adaptive study is to evaluate the efficacy and safety of ANV419 as a monotherapy and in combination with anti-PD1 antibody or anti-CTLA4 antibody in patients aged 18 years or older with advanced Cutaneous Melanoma who have previously been treated with an anti-PD-1/anti-PD-L1 antibody and/or anti-CTLA-4 antibody.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study of ANV419 as Monotherapy or in Combination With Anti-PD-1 or Anti-CTLA-4 Antibody Following Anti-PD-1/Anti-PD-L1 Antibody Treatment in Patients With Unresectable or Metastatic Cutaneous Melanoma (OMNIA-1)

Actual Study Start Date :

Dec 16, 2022

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

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
Other: ANV419 + Pembrolizumab, Q3W	Drug: ANV419 ANV419 administered by intravenous (IV) infusion Drug: Pembrolizumab Pembrolizumab administered by intravenous (IV) infusion
Other: ANV419 + Ipilimumab, Q3W	Drug: ANV419 ANV419 administered by intravenous (IV) infusion Drug: Ipilimumab Ipilimumab administered by intravenous (IV) infusion

Outcome Measures

Primary Outcome Measures

Monotherapy Dose Expansion: Objective Response Rate (ORR) as defined by RECIST v1.1 [Day 1 up to 12 months]
Combination Dose Finding: Incidence, frequency, and severity of Adverse Events with ANV419 in combination with pembrolizumab or ipilimumab [Day 1 up to 13 months]
Combination Dose Finding: Recommended Phase 2 Dose of ANV419 in combination with pembrolizumab [Day 1 up to Day 42]
Combination Dose Finding: Recommended Phase 2 Dose of ANV419 in combination with ipilimumab [Day 1 up to Day 42]
Combination Dose Expansion: Objective Response Rate (ORR) as defined by RECIST, with ANV419 in combination with pembrolizumab or ipilimumab [Day 1 up to 12 months]

Secondary Outcome Measures

Monotherapy Dose Expansion: Tumor response in terms of Objective Response Rate (ORR) assessed by iRECIST [Day 1 up to 12 months]
Monotherapy Dose Expansion: Duration of Response (DOR) according to iRECIST and iRECIST [Day 1 up to 12 months]
Monotherapy Dose Expansion: Duration of Complete Response (DCR) according to RECIST v1.1 and iRECIST [Day 1 up to 12 months]
Monotherapy Dose Expansion: Progression-free survival (PFS) according to RECIST v1.1 and iRECIST [Day 1 up to 12 months]
Monotherapy Dose Expansion: Overall survival (OS) [Day 1 up to 13 months]
Monotherapy Dose Expansion: Median Time To Response (MTT and iMTT) [Day 1 up to 12 months]
Monotherapy Dose Expansion: Incidence, frequency, and severity of Adverse Events [Day 1 up to 13 months]
Monotherapy Dose Expansion: Levels of specific anti-ANV419 antibodies in blood [Day 1 up to 12 months]
Combination Dose Finding: Serum concentration of ANV419 in blood [Day 1 up to 12 months]
Combination Dose Finding: Impact of ANV419 on the expression of markers of PBMC lineage in blood [Day 1 up to 12 months]
Combination Dose Finding: Levels of specific anti-ANV419 antibodies in blood [Day 1 up to 12 months]
Combination Dose Finding: Objective Response Rate (ORR) as defined by RECIST, with ANV419 in combination with pembrolizumab or ipilimumab [Day 1 up to 12 months]
Combination Dose Finding: Quality of life assessed with European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) [Day 1 up to 12 months]
Combination Dose Finding: 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]
Combination Dose Expansion: Incidence, frequency, and severity of Adverse Events with ANV419 in combination with pembrolizumab or ipilimumab [Day 1 up to 13 months]
Combination Dose Expansion: Quality of life assessed with European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) [Day 1 up to 12 months]
Combination Dose Expansion: 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]
Combination Dose Expansion: Levels of specific anti-ANV419 antibodies in blood [Day 1 up to 12 months]
Combination Dose Expansion: Duration of Response (DOR) according to iRECIST and iRECIST [Day 1 up to 12 months]
Combination Dose Expansion: Duration of Complete Response (DCR) according to RECIST v1.1 and iRECIST [Day 1 up to 12 months]
Combination Dose Expansion: Progression-free survival (PFS) according to RECIST v1.1 and iRECIST [Day 1 up to 12 months]
Combination Dose Expansion: Overall survival (OS) [Day 1 up to 13 months]
Combination Dose Expansion: Median Time To Response (MTT and iMTT) [Day 1 up to 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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 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 per 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. 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 investigational agent (including investigational device) 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 (eg, anti-lymphocyte-activation gene 3 antibody);
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 (defined as toxicities that required second line immunosuppression, ie, not controlled by steroids alone);
Have an LDH level of ≥2 × upper limit of normal;
Have not recovered (ie, ≤Grade 1 or at baseline with the exception of alopecia or fatigue [up to Grade 2 allowed]) from AEs resulting from prior immunotherapies. Patients who have autoimmune AEs controlled by replacement therapy (ie, hypothyroidism) due to previous treatment are eligible provided replacement therapy has been initiated and toxicity has returned to Grade 1;
Have not recovered (ie, ≤Grade 1 or at baseline) from toxicities due to a previously administered prior chemotherapy, targeted small molecule therapy, or radiation therapy; Note: If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study drug. 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 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, or 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 patient to participate, in the opinion of the treating Investigator;
Have known psychiatric or substance abuse disorders 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, starting with the Screening Visit 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: CD4+ lymphocyte count

350 µL; Had no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months; Have been on established anti-retroviral therapy for at least 4 weeks; and 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; or Note: Patients with hepatitis B (positive hepatitis B surface antigen) who have controlled infection (serum hepatitis B virus DNA by polymerase chain reaction 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 polymerase chain reaction 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.
For combination arms only: Have received solid organ or hematopoietic stem cell transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HealthPartners Institute	Bloomington	Minnesota	United States	21109A
2	CHU de Nantes	Nantes		France
3	Gustave Roussy	Paris		France
4	CHU de Poitiers	Poitiers		France
5	Hospital Clinic de Barcelona	Barcelona		Spain
6	Hospital Universitario 12 de Octubre	Madrid		Spain
7	Clínica Universidad de Navarra	Pamplona		Spain
8	Universitary Hospital Virgen Macarena	Sevilla		Spain