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

Sponsor

Anaveon AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04855929

Collaborator

(none)

Enrollment

Locations

Arms

25.2

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

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

Anticipated 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

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 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

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

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

Secondary Outcome Measures

Phase I: Objective response rate (ORR) assessed by RECIST v1.1 and iRECIST for solid tumors and IMWG2016 for multiple myeloma [Day 1 up to 12 months]
Phase II: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events [Day 1 up to 12 months]
Phase II: Objective Response Rate (ORR) assessed by iRECIST or (ORR) according to IMWG2016 [Day 1 up to 12 months]
Plasma concentration of ANV419 in blood [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 and iRECIST or IMWG2016 [Day 1 up to 12 months]
Progression-free survival (PFS) according to RECIST v1.1 and iRECIST or IMWG2016 [Day 1 up to 12 months]
Duration of response (DOR) according to RECIST v1.1 and iRECIST or IMWG2016 [Day 1 up to 12 months]
Overall survival (OS) [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country
1	Hospital Vall d'Hebrón	Barcelona	Spain
2	START Madrid, Hospital Universitario HM Sanchinarro	Madrid	Spain
3	University Hospital Basel	Basel	Switzerland
4	Cantonal Hospital St.Gallen	Saint-Gall	Switzerland
5	Royal Marsden Hospital	London	United Kingdom