Evaluation of ABP 206 Versus Nivolumab in Treatment-Naïve Patients with Unresectable or Metastatic Melanoma
- Trial ID
- 2023-503288-40-00
- Protocol
- 20210031
- Sponsor
- Amgen Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **efficacy** of ABP 206 compared with nivolumab in subjects with unresectable or metastatic melanoma who have not received prior systemic treatment for advanced disease. Evaluating efficacy is clinically relevant as it determines the potential of ABP 206 to improve patient outcomes in a population with limited treatment options.
Secondary objectives include:
- To assess the **safety** and **immunogenicity** of ABP 206 compared with nivolumab in the same patient population. These assessments are crucial for understanding the risk profile and immune response elicited by ABP 206, which are important factors in determining its suitability as a therapeutic option.
Participants
The clinical trial involves a total of **555 participants** diagnosed with **unresectable or metastatic melanoma**. The study population includes both male and female subjects who are **18 years of age or older**. Participants are required to have a histologically confirmed stage III (unresectable) or stage IV melanoma, as per the AJCC 7th edition staging system, and must have measurable disease according to RECIST version 1.1. The trial population was selected based on specific inclusion criteria, including the availability of tumor tissue for biomarker analyses and no prior systemic treatment for advanced disease. Prior adjuvant and neoadjuvant melanoma therapy is allowed if completed at least six months before randomization, and prior palliative radiotherapy is permitted if completed at least two weeks before the administration of the investigational product. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, and meet specific laboratory value criteria within 14 days prior to randomization. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, and all participants are required to provide informed consent approved by an Institutional Review Board (IRB) or Independent Ethics Committee (IEC).
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy, safety, and immunogenicity of ABP 206 compared with **OPDIVO** (nivolumab) in subjects with treatment-naïve unresectable or metastatic melanoma. The trial will involve participants who meet specific inclusion criteria, such as being 18 years or older, having histologically confirmed stage III (unresectable) or stage IV melanoma, and having measurable disease according to RECIST version 1.1. The trial is expected to last until May 2025, with participant recruitment starting in August 2023. The maximum treatment period for participants is 24 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the inclusion criteria. This visit will include assessments such as a negative serum pregnancy test for applicable female participants, laboratory evaluations, and confirmation of an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Following randomization, participants will receive either ABP 206 or OPDIVO via **intravenous administration**. Follow-up visits will be scheduled to monitor the primary endpoint of objective response by week 49, as well as secondary endpoints including objective response at week 17, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety-related endpoints such as treatment-emergent adverse events.
The end-of-study visit will occur after the completion of the treatment period or upon early termination. Conditions that may lead to early termination from the study include the occurrence of unacceptable adverse events, withdrawal of consent, or any other reason deemed necessary by the investigator. Participants' involvement is expected to last up to 24 months, depending on their response to treatment and any adverse events experienced. The trial will also assess immunogenicity-related endpoints, such as the incidence of anti-drug antibodies (ADAs), and pharmacokinetic-related endpoints, including serum concentrations of ABP 206 and nivolumab.
Treatment
The clinical trial involves the administration of two experimental medications, **OPDIVO** and **ABP 206**, both containing the active substance **nivolumab**. OPDIVO is provided as a 10 mg/mL concentrate for solution for infusion, manufactured by Bristol-Myers Squibb Pharma EEIG. It is administered via **intravenous administration**. The pharmaceutical form is a solution for infusion, and the product is subject to over-labeling and secondary packaging for investigational use. The maximum treatment period for OPDIVO is 24 months, with no specified maximum daily or total dose amount. Participant compliance is monitored through standard clinical trial procedures.
ABP 206, developed by Amgen Inc, is presented as a solution for injection in a vial. Like OPDIVO, it is administered intravenously. The pharmaceutical form is a solution for injection, and it shares the same active substance, **nivolumab**, with OPDIVO. The maximum treatment period for ABP 206 is also 24 months, with no specified maximum daily or total dose amount. The trial is designed to compare the efficacy, safety, and immunogenicity of ABP 206 against OPDIVO in subjects with treatment-naïve unresectable or metastatic melanoma. Compliance with the dosing schedule is ensured through rigorous monitoring protocols typical of clinical trials.
Efficacy
The efficacy of ABP 206 compared with **nivolumab** in subjects with unresectable or metastatic melanoma will be assessed through a series of predefined endpoints. The primary endpoint is the objective response by week 49. Secondary efficacy endpoints include objective response at week 17, progression-free survival (PFS), overall survival (OS), and duration of response (DOR). These endpoints will be measured and analyzed at specified timepoints to evaluate the treatment's impact on the disease.
Data collection will involve the use of validated scales and laboratory tests to ensure accuracy and reliability. The trial will also monitor secondary endpoints related to safety, immunogenicity, and pharmacokinetics. Safety-related endpoints will include treatment-emergent adverse events, serious adverse events, and adverse events of interest. Immunogenicity will be assessed by the incidence of anti-drug antibodies (ADAs), while pharmacokinetic endpoints will involve measuring serum trough concentrations of ABP 206 and nivolumab.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject is male or female and is ≥ 18 years of age inclusive, at the time of screening.
- Subject must have histologically confirmed stage III (unresectable) or stage IV melanoma as per AJCC (7th edition) staging system.
- Subject must have measurable disease according to RECIST (version 1.1).
- Tumor tissue from the resected site of disease must be available for biomarker analyses in order to be randomized.
- Subject has no prior systemic treatment for advanced disease. Prior adjuvant and neoadjuvant melanoma therapy is permitted if it was completed at least 6 months prior to randomization. Prior palliative radiotherapy is permitted if it was completed at least 2 weeks prior to administration of investigational product.
- For female subject (except if at least 2 years postmenopausal or surgically sterile, see Section 10.2, Appendix 2): a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Subject screening laboratory values must meet the following criteria within 14 days prior to randomization: a. White blood cell count ≥ 2000/μL b. Neutrophils ≥ 1500/μL c. Platelets ≥ 100×10³/μL d. Hemoglobin ≥ 9.0 g/dL e. Creatinine Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance > 40 mL/min as determined by Cockcroft/Gault formula: Male subject: CrCL (mL/min) = weight (kg) × (140 – age)/(72 × serum creatinine [mg/dL]) Female subject: CrCL (mL/min) = weight (kg) × (140 – age)/(72 × serum creatinine [mg/dL]) × 0.85 f. Aspartate aminotransferase (AST) ≤ 3 × ULN g. Alanine aminotransferase (ALT) ≤ 3 × ULN h. Total bilirubin ≤ 1.5 × ULN (except subjects with Gilbert Syndrome who must have total bilirubin < 3.0 mg/dL)
- Subject is capable of signing an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF) as described in Section 10.1.2, Appendix 1, before any study-specific procedures are performed.
Exclusion Criteria
- Subject has known hypersensitivity to monoclonal antibodies or to any of the excipients.
- Subject has active central nervous system (CNS) metastases not previously treated Note: subjects with adequately treated CNS metastases, radiologically and clinically stable for at least 4 weeks are permitted if they are not receiving any dose of corticosteroids or if they are receiving stable or vanishing doses of corticosteroids in equivalent less than 10 mg of prednisone Note: Neurosurgery to treat CNS metastases and adjuvant radiation after the resection of CNS are allowed
- Subject has had any prior systemic anti-cancer therapy for melanoma in the treatment of advanced or stage IV melanoma. Prior adjuvant and neoadjuvant melanoma therapy is permitted if it was completed at least 6 months prior to randomization
- Subject has ocular melanoma
- Subject has active or known immune-mediated disorders. Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll
- Subject has had prior treatment with PD-1/PD-L1 and cytotoxic T-lymphocyte-associated protein 4 inhibitors, or other antibodies targeting immune checkpoint pathways
- Subject has, per the opinion of the investigator, rapidly progressing tumor and requires treatment with faster onset than immune checkpoint inhibitors
- Subject has medical conditions requiring systemic immunosuppression with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of the first dose of investigational product. Inhaled or topical steroids permitted in the absence of active autoimmune disease
- Subject has any concurrent serious or uncontrolled medical condition (including active infection) that, in the opinion of the investigator, may increase the risk associated with study participation, investigational product administration, or would impair the ability of the subject to receive protocol therapy
- Subject has received other investigational procedures within 4 weeks prior to enrollment
- Subject has any physical or psychiatric disorder that, in the opinion of the investigator, may compromise the ability of the subject to give informed consent and/or to comply with all the required study procedures
- Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Subject has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years (subjects who had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft-versus-host disease)
- Subject has a history of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of investigational product and of low potential risk for recurrence - basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, or adequately treated carcinoma in situ without evidence of disease
- Subject has positive screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb; immunoglobulin M test only), or hepatitis C virus (HCV). Subjects with known diagnosis of HIV infection who meet the following criteria are permitted to enroll: • CD4+ T-cell counts > 350 cells/μL and without acquired immunodeficiency syndrome-defining opportunistic infections within the past 12 months. • On antiretroviral therapy for four or more weeks with a viral load of below 400 copies/mL before trial enrollment
- Subject has live vaccine therapy within 4 weeks prior to the first dose of investigational product
- Subject is a woman of childbearing potential (WOCBP) who is pregnant or breastfeeding or planning to become pregnant while participating in the study and for at least 5 months after the last dose of investigational product
- Subject is a WOCBP who is not consenting to highly effective methods of birth control (eg, true abstinence, sterilization, birth control pills, Depo Provera injections, or contraceptive implants) during treatment and for an additional 5 months after the last administration of the protocol-specified treatment
- Subject is a man with a partner of childbearing potential who does not consent to use highly effective methods of birth control (eg, true abstinence, vasectomy, or a condom in combination with hormonal birth control, or barrier methods used by the woman) during treatment and for an additional 5 months after the last administration of the protocol-specified treatment
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Croatia | Not Recruiting | 15 Aug 2023 | 11 |
 Czechia | Not Recruiting | 15 Aug 2023 | 7 |
 Estonia | Not Recruiting | 15 Aug 2023 | 30 |
 France | Not Recruiting | 15 Aug 2023 | 17 |
 Germany | Not Recruiting | 15 Aug 2023 | 40 |
 Hungary | Not Recruiting | 15 Aug 2023 | 6 |
 Italy | Not Recruiting | 15 Aug 2023 | 64 |
 Lithuania | Not Recruiting | 15 Aug 2023 | 20 |
 The Netherlands | Not Recruiting | 15 Aug 2023 | — |
 Portugal | Not Recruiting | 15 Aug 2023 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OPDIVO 10 mg/mL concentrate for solution for infusion. | Comparator | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS ADMINISTRATION | 0 | 24 | PRD6183485 |
ABP 206 | Test | SOLUTION FOR INJECTION IN VIAL | INTRAVENOUS ADMINISTRATION | 0 | 24 | PRD10108191 |