What side effects are associated with this type of intervention?

Nivolumab, a PD-1 inhibitor, is associated with side effects such as diarrhea, pneumonitis, rash, and pruritus, with severe adverse events including pneumonia. Daratumumab, a CD38 monoclonal antibody, commonly causes neutropenia, lymphocytopenia, and higher rates of infection, including pneumonia and viral reactivations like herpes zoster and CMV. Severe infections and infusion-related reactions are also notable side effects. Both treatments can lead to significant immune-related adverse events requiring careful monitoring and management.

What prior FDA approvals exist?

Daratumumab, a CD38 monoclonal antibody, has been approved by the FDA for the treatment of Multiple Myeloma, both as a monotherapy and in combination with other agents like bortezomib, melphalan, and dexamethasone. It has shown effectiveness in relapsed/refractory cases. Nivolumab, a PD-1 inhibitor, is primarily approved for other cancers such as melanoma and renal cell carcinoma, but its combination with other agents is being investigated for Multiple Myeloma. Other similar treatments include Elotuzumab, another monoclonal antibody targeting SLAMF7, and Isatuximab, another anti-CD38 monoclonal antibody, both approved for relapsed/refractory Multiple Myeloma.

What other types of research exist?

Promising novel alternatives for Multiple Myeloma treatment in 2024 include Isatuximab (another CD38 monoclonal antibody) combined with pomalidomide and dexamethasone, and Venetoclax (a Bcl-2 inhibitor) especially for patients with t(11;14) translocation. Both have shown significant efficacy in clinical trials for relapsed/refractory multiple myeloma.

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Monoclonal Antibodies

Nivolumab + Daratumumab for Multiple Myeloma

Phase 1 & 2

Waitlist Available

Research Sponsored by Bristol-Myers Squibb

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety and effectiveness of combining two drugs, nivolumab and daratumumab, in patients whose multiple myeloma has returned or did not respond to previous treatments. Nivolumab helps the immune system attack cancer, and daratumumab marks cancer cells for destruction. Nivolumab has been investigated in various cancers, including melanoma and kidney cancer, and has shown promising results.

Who is the study for?

This trial is for people with multiple myeloma who've had at least three prior treatments or whose disease resisted both proteasome inhibitors and immunomodulatory drugs. Participants must have measurable disease, be over 12 weeks post-autologous transplant, and agree to a bone marrow test.

What is being tested?

The study tests the safety and effectiveness of combining two immune therapy drugs, Nivolumab and Daratumumab, in patients with relapsed/refractory multiple myeloma to see how well they work together.

What are the potential side effects?

Potential side effects may include immune-related reactions affecting various organs, infusion-related symptoms like fever or chills, fatigue, blood count changes that can increase infection risk, and possible allergic responses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants That Experienced Drug Related Grade 3-4 AEs

Number of Participants That Experienced Drug Related Grade 3-4 SAEs

Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver

Secondary study objectives

AUC (0-T) in the Nivolumab + Daratumumab Cohort

AUC (TAU) in the Nivolumab + Daratumumab Cohort

Best Overall Response

+13 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Nivolumab monotherapy (Dose Escalation)Experimental Treatment1 Intervention

Nivolumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort

Group II: Nivolumab + LirilumabExperimental Treatment2 Interventions

Non-randomized Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks Enrollment is closed for this cohort

Group III: Nivolumab + IpilimumabExperimental Treatment2 Interventions

Nivolumab and Ipilimumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort

Group IV: Nivo + Dara + Pom + Dexa vs. Nivo + DaraExperimental Treatment4 Interventions

Randomized Nivolumab: Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 \& beyond: 480 mg Day 1 Daratumumab: Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 \& beyond: 16 mg/kg Day 1 Pomalidomide: 4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle Dexamethasone: Weeks without daratumumab dosing: * 40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old * 20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants \> 75 years old Weeks with daratumumab dosing: * 20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old * 16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants \> 75 years old Enrollment is closed for this cohort

Group V: Daratumumab vs. Nivolumab + DaratumumabExperimental Treatment2 Interventions

Randomized Nivolumab: Cycle 1: 240 mg Day 15 Cycle 2 \& beyond: 480 mg Day 1 Daratumumab: Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 \& beyond: 16 mg/kg Day 1

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dexamethasone

2007

Completed Phase 4

~2650

Pomalidomide

2011

Completed Phase 2

~1020

Nivolumab

2014

Completed Phase 3

~5220

Ipilimumab

2014

Completed Phase 3

~3140

Lirilumab

2017

Completed Phase 2

~740

Daratumumab

2014

Completed Phase 3

~2000

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Nivolumab, a PD-1 inhibitor, enhances the immune system's ability to attack cancer cells by blocking the PD-1 pathway, which myeloma cells use to evade immune detection. Daratumumab, a CD38 monoclonal antibody, targets the CD38 protein on myeloma cells, inducing cell death through immune-mediated cytotoxicity and direct apoptosis. These mechanisms are significant for Multiple Myeloma patients as they leverage the immune system to combat the disease, potentially leading to better treatment outcomes and new therapeutic options.