Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAlfred Chung, MD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
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.)
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
Talquetamab
Biological/VaccineGiven subcutaneously (SQ)
Iberdomide
DrugGiven orally (PO)
Dexamethasone
DrugGiven PO
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Treatment groups
32 Participants
are divided into 3 treatment groupsGroup A: Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone) - Starting DoseExperimental treatment 4 interventions
Group B: Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone)Experimental treatment 4 interventions
Group C: Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
Up to 1 cycle (Cycles are 28 days in length)2
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.
Time frame
Up to 1 cycle (Cycles are 28 days in length)3
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).
Time frame
Up to 1 cycle (Cycles are 28 days in length)4
Proportion of participants experiencing Dose-Limiting Toxicity (DLTs) (Dose Expansion Cohort)
The frequency, type, and severity (grade) of each DLT will be reported
Time frame
Up to 3 yearsSecondary outcomes
1
Objective response rate (ORR) (Dose Escalation Cohorts)
ORR will be defined as all responses greater than or equal to a partial response (i.e., PR, VGPR, CR, or sCR per IMWG definition). Will be summarized using frequency and percentage, along with 95% CIs.
Time frame
Up to 3 years2
Number of participants achieving VGPR or CR and MRD (negative (-)) response
MRD will be defined as achieving ≥ VGPR and MRD (-) response will be defined as having \< 1 multiple myeloma clone per 100,000 bone marrow cells (10-5) by next-generation sequencing (NGS) (clono sequence (seq); 10-5). Will be reported for the entire population and for those treated at the MTD.
Time frame
Up to 3 years3
Proportion of participants with treatment-related adverse events
Toxicity will be measured by CTCAE version 5.0; cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) will be assessed according to the American Society for Transplantation and Cellular Therapy guidelines; neurological treatment-emergent adverse events that are not assessed as ICANS should be graded per CTCAE version 5.0 and managed by per institutional guidelines.
Time frame
Up to 3 years4
Changes in scores on the European Organization for Research and Treatment of Cancer - Quality of Life questionnaire (EORTC-QLQ-C30) over time
The functional domains measure the quality of life in Physical functioning, Role functioning, Emotional functioning, Cognitive functioning, Social functioning. Scores consists of responses to items with responses ranging from 1="Not at all" to 4="Very Much". The raw score is calculated by estimating the mean of the items that make up each domains with a resulting total range of 1 - 4. These scores are then transformed to standardized scale score, so that scores range from 0 to 100. A high score for the functional domains represents a high level of functioning.
Time frame
Up to 3 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Alfred Chung, MD
Lead sponsor
University of California, San Francisco
Sponsor institution
Janssen Research & Development, LLC
Collaborator
Celgene Corporation
Collaborator
Source ClinicalTrials.gov