A Study to Compare the PK Characteristics, Safety, Tolerability, and Immunogenicity of HLX15-SC With DARZALEX FASPRO® in Combination With Lenalidomide and Dexamethasone (Rd) in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma

Exclusion Criteria28

• Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• Patient has plasma cell leukemia (according to IMWG criterion: ≥ 5% of plasma cells in the peripheral blood and/or an absolute plasma cell count of ≥ 2 x 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Patient has prior or current systemic therapy or ASCT for MM, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before randomization.
• Patient has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 6.
• Patient has a history of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence within 3 years).
• Patient has clinical signs of meningeal involvement of MM.
• Patient has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] < 50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years. Patient with known or suspected COPD or asthma must have a FEV1 test during screening.
• Patient is known to be seropositive for history of human immunodeficiency virus (HIV) or known to have treponema pallidum antibodies (Anti-TP).
• Patient is known to have active hepatitis B or C.
• Patient is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Patients with resolved infection (that is, patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[Anti-HBc\] and/or antibodies to hepatitis B surface antigen \[Anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded.
• EXCEPTION: Patients with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Patient is seropositive for hepatitis C must be screened using PCR measurement of hepatitis C virus (HCV) ribonucleic acid (RNA) levels. Those who are PCR positive will be excluded.
• Patient has any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
• Patient has clinically significant cardiac disease, including:
• Myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association \[NYHA\] Class III-IV ).
• Cardiac arrhythmia (NCI-CTCAE Version 6 Grade ≥ 2) or clinically significant ECG abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) (See Appendix 6) > 470 ms.
• Patient has known allergies, hypersensitivity, or intolerance to lenalidomide, corticosteroids, monoclonal antibodies or human proteins, or their excipients or known sensitivity to mammalian-derived products.
• Patient has history of drug abuse or substance abuse one year prior to randomization. Patient is known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder).
• Patient is a woman who is pregnant, or breast-feeding, or planning to become pregnant or donate eggs (ova, oocytes) while enrolled in this study or within 140 days after the last dose of study products.
• Or patient is a man who plans to father a child and/or donate sperm while enrolled in this study or within 140 days after the last dose of study products.
• Patient does not agree to abstain completely from sexual intercourse, or plan to use a contraceptive method that is not acceptable to the investigator (unacceptable methods of contraception include: i. periodic abstinence \[such as calendar method, ovulation method, basal body temperature method, post-ovulation safety period method, etc.\], withdrawal, etc.; ii. medical contraceptive measures such as oral contraceptives, contraceptive injections, contraceptive patches, subcutaneous implantation, intrauterine hormone contraceptive devices, local contraceptives such as spermicides, etc.).
• Patient had radiation therapy within 14 days of randomization.
• Patient had plasmapheresis within 28 days of randomization.
• Patient had a history of blood donation or total blood loss of 200 mL or more within 3 months before randomization.
• Patient had major surgery within 28 days before randomization or has not fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study or within 28 days after the last dose of study treatment. Kyphoplasty is not considered major surgery.
• Patient in clinical trials of any other drug or device within 3 months (or 5 half-lives of the corresponding investigational product if the half-life of the drug is long \[5 half-lives > 3 months\]) before randomization.
• Patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments