HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the [LYNOZYFIC Prescri…
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the LYNOZYFIC Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
LYNOZYFIC (linvoseltamab-gcpt) lin-oh-ZI-fik Regeneron Pharmaceuticals, Inc. **Original Approval date: **July 2, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
LYNOZYFIC is a bispecific antibody used to treat a type of cancer called multiple myeloma. LYNOZYFIC is indicated for adults whose cancer has come back after, or not responded to, at least four prior treatment regimens including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody (mAb). This is called relapsed or refractory disease.
How is this drug used?
LYNOZYFIC is given as an infusion through a vein by a healthcare provider. A process called step up dosing is used where the first dose is low dose. This is done to evaluate how well the patient tolerates the drug before the first full-strength dose is administered. Patients who receive LYNOZYFIC will be hospitalized for 24 hours after receiving each of the first two step up doses to be closely monitored for side effects. After completing these two doses, patients will receive full doses once a week.
Who participated in the clinical trial?
The FDA approved LYNOZYFIC based on the safety and efficacy data from a single clinical trial (Study R5458-ONC-1826). A total of 117 patients who received the full dose of the drug (200 mg) were included in the safety analysis population. The efficacy population included 80 patients who received the full dose and had at least four prior lines of therapy for their disease.
The patients in the efficacy population were treated in five countries including Belgium, Germany, Spain, Korea, and the United States. A total of 77% of patients were enrolled at study sites in the United States. A total of 22% of patients were enrolled at sites outside the United States (Europe 11% and Asia 11%). Males comprised 64% of the total efficacy population. Regarding the race of patients in the United States study population, 77% were White, 12% were Black or African American, 1% Asian, and 2% were identified as “other” or not reported. Only 2% of United States patients identified their ethnicity as Hispanic. The average age of the patients was 63 years old (range 37 to 83 years).
How were the trials designed?
The R5458-ONC-1826 clinical trial was a phase 1/2 single-arm study of LYNOZYFIC monotherapy (given alone) in patients with relapsed or refractory multiple myeloma. Phase 1 was the dose escalation portion to determine the appropriate dosing and learn about the side effects of the drug. Phase 2 included two groups (“cohorts”) to evaluate the efficacy of the proposed dose. All study patients received LYNOZYFIC until their disease progressed or the side effects became too toxic.
The benefit and effectiveness of LYNOZYFIC was measured by the proportion of patients that achieved a clinically relevant improvement in their disease (overall response rate; ORR) based on standard response criteria and how long the response lasted (duration of response; DOR).
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of LYNOZYFIC.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of LYNOZYFIC.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of LYNOZYFIC.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of LYNOZYFIC.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
MORE INFO
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population
DemographicLYNOZYFIC N=80
Sex, n (%) Male51 (64) Female29 (36) Age, years Median (min, max)71 (37, 83) Age group, years, n (%) <6527 (34) ≥65 to <7529 (36) ≥7524 (30) Race, n (%) White55 (69) Black or African American11 (14) Asian10 (13) Other1 (1.3) Not reported3 (3.8) Ethnicity, n (%) Not Hispanic or Latino72 (90) Hispanic or Latino2 (2.5) Not reported6 (8)
Source: Adapted from FDA Review
What are the benefits of this drug?
The benefit of LYNOZYFIC was measured by the proportion of patients that achieved a clinically relevant improvement in their disease (ORR). Response was analyzed using the International Myeloma Working Group (IMWG) Criteria. The ORR was 70%.
MORE INFO
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Efficacy Results, Best Overall Response per IMWG, Efficacy Population
ResponseLYNOZYFIC N=80
BOR per IMWG criteria, n (%) sCR31 (38.8) CR5 (6.3) VGPR15 (18.8) PR5 (6.3) Response per IMWG criteria ORR (sCR+CR+VGPR+PR), n (%)56 (70.0) 95% CI for ORR58.7, 79.7
Source: Adapted from FDA Review
Abbreviations: : BOR, best overall response; CI, confidence interval; CR, complete response; IMWG, International Myeloma Working Group; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The observed effect of LYNOZYFIC was larger in females than males. Because of the limited number of patients, this difference may be due to chance.
- **Race: **Most patients were White. Differences in effectiveness among races could not be determined because of the small number of patients in other races.
- Age: No overall differences in effectiveness of LYNOZYFIC were observed in patients of different age groups.
MORE INFO
Were there any differences in how well the drug worked in clinical trials among sex, race and age groups?
Table 3 summarizes subgroup analysis of ORR. Because the number of patients in each subgroup was relatively small, the subgroup analyses are considered exploratory.
Table 3. Efficacy Results, Overall Response Rate per IMWG Criteria by Subgroup, Efficacy Population
SubgroupORR* N=80 n/Ns (%)95% CI
Number of patients with ≥PR56/80 (70.0)58.7, 79.7 Sex Male30/51 (58.8)44.2, 72.4 Female26/29 (89.7)72.6, 97.8 Race White39/55 (70.9)57.1, 82.4 Black or African American9/11 (81.8)48.2, 97.7 Other8/14 (57.1)28.9, 82.3 Age group, years <6515/27 (55.6)35.3, 74.5 ≥65 to <7523/29 (79.3)60.3, 92.0 ≥7518/24 (75.0)53.3, 90.2
Source: Adapted from FDA Review * ORR includes: stringent complete response + complete response + very good partial response + partial response Abbreviations: CI, confidence interval; ITT, intent-to-treat; n, number of subjects with non-missing assessments at both Baseline and Day 14 visit
What are the possible side effects?
Side effects of LYNOZYFIC were evaluated in the safety population consisting of 117 patients who received the full dose (200 mg). The most common adverse reactions (≥20%) were musculoskeletal pain, cytokine release syndrome (CRS), cough, diarrhea, upper respiratory tract infection, fatigue, pneumonia, nausea, and headache. The most common National Cancer Institute Common Toxicology Criteria (NCI CTC) Grade 3 or 4 laboratory abnormalities (≥30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, and decreased white blood cells. Serious adverse events occurred in 74% of patients. Adverse events leading to dose interruption occurred in 71% of patients, most commonly neutrophil decrease, and infections. Adverse events leading to treatment discontinuation occurred in 16%, most commonly infections.
The key safety concerns for LYNOZYFIC are CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and neurologic toxicity were common occurrences in the safety population, occurring in 46% and 54% of patients, respectively. A boxed warning for both events has been incorporated in the LYNOZYFIC** **U.S. Prescribing Information (USPI). Other safety concerns identified in the USPI Warnings and Precautions section include infections, low neutrophil count (neutropenia), and liver disorders (hepatotoxicity).
MORE INFO
What are the possible side effects (results of trials used to assess safety)?
Table 4. Adverse Reactions (>10%) of Patients, Safety Population
Adverse ReactionLYNOZYFIC, N=117 All Grades %Grade 3 or 4 %
Musculoskeletal and connective tissue disorders Musculoskeletal pain533.4 Immune system disorders Cytokine release syndrome460.9 Hypogammaglobulinemia130.9 Respiratory, thoracic, and mediastinal disorders Cough390 Dyspnea210.9 Nasal congestion160 Infections and infestations Upper respiratory tract infection356 Pneumonia2821 COVID-19175 Urinary tract infections168 Sepsis106 Gastrointestinal disorders Diarrhea351.7 Nausea230 Vomiting190 Constipation170 General disorders and administration site conditions Fatigue340 Edema190.9 Pyrexia170 Nervous system disorders Headache220.9 Encephalopathy183.4 Sensory neuropathy130.9 Metabolism and nutrition disorders Decreased appetite150.9 Skin and subcutaneous tissue disorders Rash151.7 Psychiatric disorders Insomnia130 Vascular disorders Hypertension104.3
Source: Adapted from FDA Review
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- **Sex: **No overall differences in side effects of LYNOZYFIC were observed between females and males.
- Race: All patients experienced similar side effects regardless of race.
- **Age: **No overall differences in safety or effectiveness were observed in patients of different age groups.
MORE INFO
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Treatment-Emergent Adverse Events by Gender, Safety Population
| Parameter | LYNOZYFIC, N=117 | Male N=64 n (%) | Female N=53 n (%) |
|---|---|---|---|
| Any grade TEAEs | 64 (100) | 53 (100) | |
| Grade 3 to 4 TEAEs | 48 (75) | 48 (91) | |
| Grade 5 (fatal) TEAEs | 10 (16) | 4 (7.5) | |
| Serious TEAEs | 49 (77) | 37 (70) | |
| AE leading to discontinuation | 11 (17) | 8 (15) | |
| AE leading to dose interruption | 42 (66) | 41 (77) | |
| AE leading to dose reduction | 8 (12) | 8 (15) |
Source: Adapted from FDA Review *Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event *
Table 6. Treatment-Emergent Adverse Events by Race, Safety Population
| Parameter | LYNOZYFIC, N=117 | White N=83 n (%) | Black or African American N=20 n (%) | Asian N=10 n (%) | Other N=4 n (%) |
|---|---|---|---|---|---|
| Any grade TEAEs | 83 (100) | 20 (100) | 10 (100) | 4 (100) | |
| Grade 3 to 4 TEAEs | 66 (79) | 20 (100) | 6 (60) | 4 (100) | |
| Grade 5 (fatal) TEAEs | 8 (10) | 3 (15) | 2 (20) | 1 (25) | |
| Serious TEAEs | 60 (72) | 17 (85) | 5 (50) | 4 (100) | |
| AE leading to discontinuation | 12 (14) | 4 (20) | 1 (10) | 2 (50) | |
| AE leading to dose interruption | 57 (69) | 16 (80) | 7 (70) | 3 (75) | |
| AE leading to dose reduction | 12 (14) | 1 (5) | 2 (20) | 1 (25) |
Source: Adapted from FDA Review *Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event *
Table 7. Treatment-Emergent Adverse Events by Age, Safety Population
| Parameter | LYNOZYFIC, N=117 | <65 Years N=44 n (%) | ≥65 Years N=73 n (%) | ≥75 Years N=31 n (%) |
|---|---|---|---|---|
Any grade TEAEs | 44 (100) | 73 (100) | 31 (100) | |
Grade 3 to 4 TEAEs | 38 (86) | 58 (80) | 24 (77) | |
Grade 5 (fatal) TEAEs | 5 (11) | 9 (12) | 6 (19) | |
Serious TEAEs | 37 (84) | 49 (67) | 21 (68) | |
AE leading to discontinuation | 7 (16) | 12 (16) | 5 (16) | |
AE leading to dose interruption | 28 (64) | 55 (75) | 26 (84) | |
AE leading to dose reduction | 6 (14) | 10 (14) | 5 (16) |
Source: Adapted from FDA Review *Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event *
GLOSSARY
**CLINICAL TRIAL: **Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
**COMPARATOR: **A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
**EFFICACY: **How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
**PLACEBO: **An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
**SUBGROUP: **A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.