Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma

NCT06348108 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 232514NCI-2024-01992
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial will evaluate the safety, side effects, and best dose of talquetamab in combination with iberdomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). There is currently a significant unmet need for patients with relapsed or refractory multiple myeloma (RRMM) who are triple class refractory and have been exposed to B-cell maturation antibody (BCMA) targeted therapy. These patients currently have limited treatment options and poor survival. Talquetamab is an FDA approved drug that can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an investigational drug and works by targeting and destroying proteins that help myeloma cancer cells to survive. Dexamethasone is a corticosteroid, is similar to a natural hormone produced by the adrenal glands to reduce inflammation (swelling, heat, redness, and pain) and is used to in helping to treat certain types of cancer including myeloma.

Conditions

Relapsed Multiple Myeloma; Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• Proportion of participants reporting treatment-emergent adverse events (AEs) (Dose Escalation Cohorts)

  Safety will be evaluated for the population of participants who received at least one dose of study drug. Treatment-emergent AEs will be graded by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 1 cycle (Cycles are 28 days in length)

• Proportion of participants experiencing Dose-Limiting Toxicity (DLTs) (Dose Escalation Cohorts)

  Maximum tolerated dose (MTD) will be defined as the highest dose at which no more than one instance of DLT is observed among 6 participants treated.

  Up to 1 cycle (Cycles are 28 days in length)

• Recommended phase 2 dose (RP2D) (Dose Escalation Cohorts)

  RP2D will be defined as the MTD to be evaluated in the expansion cohort based on safety and preliminary activity of at least 2 dose levels (6 patients treated/dose level).

  Up to 1 cycle (Cycles are 28 days in length)

• Proportion of participants experiencing Dose-Limiting Toxicity (DLTs) (Dose Expansion Cohort)

  The frequency, type, and severity (grade) of each DLT will be reported

  Up to 3 years

• Objective response rate (ORR) (Dose Expansion Cohort)

  ORR will be defined as all responses greater than or equal to a partial response (PR) (i.e., PR, very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) per International Myeloma Working Group (IMWG) definition). Under Simon's two-stage design, final efficacy evaluation for the primary endpoint will calculate the uniformly minimum variance unbiased estimator, p-value and 95% CI for the response rates.

  Up to 3 years

Secondary Outcomes (5)

• Objective response rate (ORR) (Dose Escalation Cohorts)

  Up to 3 years

• Number of participants achieving VGPR or CR and MRD (negative (-)) response

  Up to 3 years

• Proportion of participants with treatment-related adverse events

  Up to 3 years

• Changes in scores on the European Organization for Research and Treatment of Cancer - Quality of Life questionnaire (EORTC-QLQ-C30) over time

  Up to 3 years

• Changes in scores on the EORTC QLQ- Multiple Myeloma Questionnaire (EORTC-QLQ-M20) over time

  Up to 3 years

Study Arms (3)

Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting Dose

EXPERIMENTAL

Participants receive 0.8 mg/kg Talquetamab (Tal) subcutaneously (SQ) over 1-3 minutes every 2 weeks (days 1 and 15 of each cycle), 0.75 mg Iberdomide orally (PO) once a day (QD) on days 1-21 of each 28-day cycle, and 20-40mg of Dexamethasone PO weekly, but may be continued at the discretion of the investigator. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo bone marrow biopsy, skeletal x-ray, CT, Positron Emission Tomography (PET)/CT, or MRI, tissue and blood sample collection throughout the study.

Biological: Talquetamab; Drug: Iberdomide; Drug: Dexamethasone; Procedure: Bone Marrow Biopsy

Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone)

EXPERIMENTAL

Participants receive 0.8 mg/kg Talquetamab (Tal) subcutaneously (SQ) over 1-3 minutes every 2 weeks (days 1 and 15 of each cycle), 1.0 mg Iberdomide orally (PO) once a day (QD) on days 1-21 of each 28-day cycle, and 20-40mg of Dexamethasone PO weekly, but may be continued at the discretion of the investigator. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo bone marrow biopsy, skeletal x-ray, CT, Positron Emission Tomography (PET)/CT, or MRI, tissue and blood sample collection throughout the study.

Biological: Talquetamab; Drug: Iberdomide; Drug: Dexamethasone; Procedure: Bone Marrow Biopsy

Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)

EXPERIMENTAL

Participants receive the recommended phase 2 dose of Iberdomide in combination with Talquetamab and 20-40mg of Dexamethasone which may be continued at the discretion of the investigator. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo bone marrow biopsy, imaging scans, tissue and blood sample collection throughout the study.

Biological: Talquetamab; Drug: Iberdomide; Drug: Dexamethasone; Procedure: Bone Marrow Biopsy

Interventions

Iberdomide DRUG

Given orally (PO)

Also known as: CELMoD, CC-220, 1323403-33-3

Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone); Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting Dose; Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)

Dexamethasone DRUG

Given PO

Also known as: Decadron, DexPak, Hemady

Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone); Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting Dose; Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy

Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone); Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting Dose; Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)

Talquetamab BIOLOGICAL

Given subcutaneously (SQ)

Also known as: Anti-CD3/Anti-GPRC5D Bispecific Monoclonal Antibody JNJ-64407564, DuoBody Antibody JNJ-64407564

Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone); Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting Dose; Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age.
• Has a prior history of (h/o) MM (based on International Myeloma Working Group (IMWG) criteria) and now has evidence of relapsed or refractory MM. RRMM of progressive disease as defined by the IMWG 2006 and 2016 criteria (Kumar at al).
• Specific criteria for dose escalation and dose expansion:
• Phase 1 dose escalation: patients will be required to have TCE RRMM (including a proteasome inhibitor (PI) (≥ 2 cycles or 2 months of treatment), an immunomodulatory drug (IMiD)) (≥ 2 cycles or 2 months of treatment) and a CD38 antibody (≥ 2 cycles or 2 months of treatment) after receiving ≥ 3 prior lines of therapy. Prior BCMA exposure is allowed. (Subjects with discontinued PI/IMiD/Cluster of differentiation 38 (CD38) therapy due to severe adverse event after \< 2 months are allowed)
• Dose expansion cohort: RRMM patients will be lenalidomide refractory, TCE (exposed to IMiD, PI and CD38 antibody therapy (≥ 2 cycles or 2 months of treatment for each) and have received ≥ 2 prior lines of therapy. Prior BCMA targeted therapy is allowed, not required. (Subjects with discontinued PI/IMiD/CD38 therapy due to severe adverse event after \< 2 months are allowed. Lenalidomide refractory is defined as having evidence of progressive disease on lenalidomide (≥ 10 mg or greater, ≥ 21 days/28) or within 60 days of stopping lenalidomide therapy.)
• Has measurable disease defined as at least 1 of the following:
• Serum M-protein ≥ 0.5 g/dL (dose escalation) and 1.0 g/dL (dose expansion cohorts)
• Urine M-protein ≥ 200 mg/24 hours
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate baseline organ function, as demonstrated by the following:
• Calculated creatinine clearance \> 30 mL/min as assessed by the Cockcroft-Gault equation, Modification of Diet in Renal Disease (MDRD) equation (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2015) or as assessed by 24-hour urine collection.
• Serum bilirubin ≤ 1.5 mg/dL, excluding Gilbert's.
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × institutional upper limit normal (ULN).
• Total serum calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) (treatment of hypercalcemia is allowed and patients may enroll if hypercalcemia returns to WNL with standard treatment).
• Has adequate baseline hematologic function, as demonstrated by the following:

You may not qualify if:

• Has persistent clinically significant toxicities (grade ≥ 2; per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) from previous anticancer therapy (excluding alopecia which is permitted and excluding grades 2 and 3 laboratory abnormalities (including hematologic abnormalities) if participants are not associated with symptoms, are not considered clinically significant by the investigator, and can be managed with available medical therapies.
• Has NCI CTCAE grade ≥ 3 peripheral neuropathy from any etiology or grade ≥ 2 peripheral neuropathy with pain.
• Has received treatment with cytotoxic (alkylators) within 3 weeks, biologic (IMiDs/PIs) within 2 weeks, targeted therapies (monoclonal antibodies) within 4 weeks, chimeric antigen receptor (CAR) T-cell (CAR-T)or autologous stem cell transplant therapy within 3 months or any novel therapy within 5- 1/2 lives of therapy.
• Has had radiation therapy within 14 days of first dose of study therapy, unless less than 5% marrow exposure, then no limit.
• Has had any prior GPRC5D targeted bispecific antibody therapy or GPRC5D CAR-T therapy or has had previous treatment with Iber.
• Has any active or uncontrolled infection including any viral, bacterial or fungal infection; and/or HIV, active hepatitis (Hep) C and active Hep B (hepatitis B (HB) surface antigen (HBsAg) (+), HB core antigen (HBcAb) (+) or (+) Hep B deoxyribonucleic acid (DNA) by polymerase chain reaction (pcr), Hep C ribonucleic acid (RNA) (+) by pcr. Patients who have received Intravenous immunoglobulin therapy (IVIG) replacement therapy may have (+) HBcAb results from the IVIG therapy. These patients can enroll if Hep B DNA by pcr test is negative. These patients need to be on antiviral therapy and be monitored for hepatitis B virus (HBV) DNA throughout study therapy per local guidelines and as clinically indicated.
• Has an additional active malignancy that may confound the assessment of the study endpoints. If the patient has a past cancer history (active malignancy within 2 years before study entry) with substantial potential for recurrence, this must be discussed with the sponsor/investigator before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: nonmelanoma skin cancer and carcinoma in situ (including transitional cell carcinoma, cervical cancer, anal carcinoma, ductal carcinoma in situ (DCIS) and melanoma in situ), any cancer resected with curative intent, low-grade cancer not requiring therapy.
• Is pregnant or breast feeding.
• Has clinically significant cardiovascular disease including, albeit not limited to:
• Uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure
• Uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months before study entry
• Uncontrolled hypertension or clinically significant arrhythmias not controlled by medication.
• Has active POEMS (polyneuropathy, organomegaly, endocrinopathy/edema, monoclonal-protein, skin syndrome), amyloid light (AL) amyloidosis, primary plasma cell leukemia or active central nervous system (CNS) or parenchymal/leptomeningeal myeloma.
• Has uncontrolled, clinically significant organ dysfunction that in the opinion of the investigator would put the patient at significant risk for toxicity from study therapy.
• Has recent major surgery within 4 weeks or significant gastrointestinal (GI) disease that would interfere with GI absorption of oral medications.

Sponsors & Collaborators

• Alfred Chung, MD: lead
• Janssen Research & Development, LLC: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

University of Calfornia, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

talquetamab; iberdomide; Dexamethasone; Calcium Dobesilate; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alfred Chung, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Hematopoietic Malignancies Clinical Trial Recruitment

CONTACT

877-827-3222; HDFCCC.Heme@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: April 4, 2024
• Study Start: July 28, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)