Trial Title:
Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma
NCT ID:
NCT06348108
Condition:
Multiple Myeloma
Refractory Multiple Myeloma
Relapsed Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Antibodies
Immunoglobulins
Antibodies, Bispecific
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Talquetamab
Description:
Given subcutaneously (SQ)
Arm group label:
Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: DL 3 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)
Other name:
Anti-CD3/Anti-GPRC5D Bispecific Monoclonal Antibody JNJ-64407564
Other name:
DuoBody Antibody JNJ-64407564
Intervention type:
Drug
Intervention name:
Iberdomide
Description:
Given orally (PO)
Arm group label:
Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: DL 3 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)
Other name:
CELMoD
Other name:
CC-220
Other name:
1323403-33-3
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given PO
Arm group label:
Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: DL 3 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)
Other name:
Decadron
Other name:
DexPak
Other name:
Hemady
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Dose Escalation Cohort: DL 2 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: DL 3 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Escalation Cohort: Dose Level (DL) 1 (Talquetamab, Iberdomide, Dexamethasone)
Arm group label:
Dose Expansion Cohort (Talquetamab, Iberdomide, Dexamethasone)
Other name:
Biopsy
Summary:
This phase I trial tests 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 approved for
use by the Food and Drug Administration (FDA) to treat RRMM when given alone. Talquetamab
can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an
investigational drug. Iberdomide 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. It relieves inflammation (swelling, heat,
redness, and pain) and is used to treat certain types of cancer including myeloma. Giving
talquetamab in combination with iberdomide and dexamethasone may be safe, tolerable and
effective in treating patients with RRMM
Detailed description:
PRIMARY OBJECTIVES:
I. To assess safety of the combination of talquetamab (Tal), iberdomide (Iber) and
dexamethasone (Dex) in patients with triple class exposed (TCE) RRMM. (Phase 1b-dose
escalation (DE)).
II. To assess dose limiting toxicity (DLT) and determine the recommended phase 2 dose
(RP2D) of the combination of Tal, Iber and Dex administered in 28-day cycles in patients
with TCE RRMM. (Phase 1b-DE) III. To further assess safety of RP2D of the combination of
Tal, Iber and Dex administered in 28-day cycles in patients with TCE RRMM Len-refractory,
and having received >= 2 prior lines of therapy. (Phase 1b-expansion (Exp)) IV. To assess
overall response rate (ORR) in patients with TCE RRMM, Len-refractory, and having
received ≥ 2 prior lines of therapy. (Phase 1b-Exp).
SECONDARY OBJECTIVES:
I. To assess ORR, and to determine minimal residual disease (MRD) negative (-) rates in
patients achieving ≥ very good partial remission (VGPR).
II. To assess toxicity (incidence of adverse events (AEs), serious AEs (SAEs), and
treatment discontinuation due to toxicity) and safety (physical examination findings,
vital signs, and clinical laboratory evaluations) in patients with RRMM.
III. Describe changes in health-related quality of life (HRQoL) using the European
Organization for Research and Treatment of Cancer (C30) -Quality of Life questionnaire
(QLQ) (EORTC-QLQ-C30) and EORTC QLQ-Multiple Myeloma Questionnaire (MY20)).
EXPLORATORY OBJECTIVES:
I. To assess serial cytokines levels with treatment of the combination of Tal, Iber and
Dex and predictive values of response, cytokine release syndrome (CRS) and other adverse
events.
II. To assess changes in immune cells in blood and bone marrow with treatment of the
combination of Tal, Iber and Dex.
III. To determine the efficacy of combination of Tal, Iber and Dex defined as achieving
complete response (CR) and MRD (-) status and correlation between mass spectroscopy and
bone marrow (BM) MRD assessments.
OUTLINE: This is a dose-escalation study of Iber followed by a dose-expansion study.
Patients receive Tal subcutaneous (SQ) over 1-3 minutes on days 1, 4, 8, and 15 of cycle
1, days 1 and 15 of cycles 2-6, and day 1 of cycle 7 and subsequent cycles, Iber orally
(PO) once daily (QD) on days -7 thru day 14 of cycle 1 and days 1-21 of cycle 2 and
subsequent cycles, and Dex PO on days 1, 4, 8, 15, and 22 of cycle 1 and on days 1, 8,
15, and 22 of cycles 2-4, but may be continued at the discretion of the investigator.
Treatment repeats every 35 days for cycle 1 and then every 28 days for subsequent cycles
in the absence of disease progression or unacceptable toxicity. Patients also undergo
bone marrow biopsy, skeletal x-ray, computed tomography (CT), positron emission
tomography (PET)/CT, or magnetic resonance imaging (MRI), tissue and blood sample
collection throughout the study.
After completion of study treatment, patients are followed up at 30 days every 8 weeks
for up to 2 years or until progression or initiation of subsequent therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female ≥ 18 years of age.
2. 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).
3. Specific criteria for dose escalation and dose expansion:
1. 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)
2. 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.)
4. Has measurable disease defined as at least 1 of the following:
1. Serum M-protein ≥ 0.5 g/dL (dose escalation) and 1.0 g/dL (dose expansion
cohorts)
2. Urine M-protein ≥ 200 mg/24 hours
3. Serum free light chain (FLC) assay: involved FLC assay ≥ 10 mg/dL (≥ 100 mg/L)
AND an abnormal serum FLC ratio (< 0.26 or > 1.65). (Can be used to fulfill the
inclusion criteria of measurable disease in patients who do not have measurable
disease by M-protein).
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Has adequate baseline organ function, as demonstrated by the following:
1. 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.
2. Serum bilirubin ≤ 1.5 mg/dL, excluding Gilbert's.
3. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 ×
institutional upper limit normal (ULN).
4. 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).
7. Has adequate baseline hematologic function, as demonstrated by the following:
1. Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L (myeloid growth factors must not
have been administered within 7 days (14 days for extended 1/2-life products).
2. Hemoglobin ≥ 8 g/dL (red blood cell transfusions permitted provided the anemia
is disease-related).
3. Platelet count ≥ 100 x 10^9/L and no platelet transfusions during the 7 days
before first dose (without transfusions). (Dose expansion cohorts will be
allowed to have platelets counts ≥ 75 x 10^9/L with no platelet transfusions
during the prior 7 days).
8. Must have at least 2 negative serum beta-human chorionic gonadotropin (β-hCG)
pregnancy test result obtained prior to initiating therapy. The first test should be
performed within 10-14 days and the second within 24 hours prior to initiating
therapy if the patient is a female of childbearing potential (FCBP; defined as a
sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy
or has not been naturally postmenopausal for at least 24 consecutive months).
9. Men and women of childbearing potential must agree to not donate sperm and eggs (ova
and oocytes) throughout study therapy and for 3 months after the last treatment.
10. Men and women agree to use acceptable contraceptive methods for the duration of time
on the study, and continue to use acceptable contraceptive methods for 3 months
after the last treatment with study treatment.
1. Women of childbearing potential must agree to 2 methods of reliable birth
control simultaneously while receiving study treatment and until 100 days after
last dose of study treatment: one highly effective form of contraception (tubal
ligation, intrauterine device, hormonal [oral, injectable, transdermal patches,
vaginal rings or implants] or partner's vasectomy, and 1 additional effective
contraceptive method (male latex or synthetic condom, diaphragm or cervical
cap).
2. Males must agree to always use a latex or synthetic condom during any sexual
contact with females of reproductive potential.
11. All patients should be encouraged to be fully vaccinated prior to initiation of
therapy including being up-to-date on vaccines against pneumococcus, yearly
influenza, Coronavirus disease (COVID) booster(s), and any age appropriate vaccine.
Live attenuated vaccines are not allowed while on study treatment or within 4 weeks
of starting treatment.
12. Has provided signed informed consent before initiation of any study-specific
procedures or treatment.
13. Must agree to, and be capable of, adhering to the study visit schedule and other
protocol requirements, including follow-up for overall survival.
Exclusion Criteria:
1. 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.
2. Has NCI CTCAE grade ≥ 3 peripheral neuropathy from any etiology or grade ≥ 2
peripheral neuropathy with pain.
3. 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.
4. Has had radiation therapy within 14 days of first dose of study therapy, unless less
than 5% marrow exposure, then no limit.
5. Has had any prior GPRC5D targeted bispecific antibody therapy or GPRC5D CAR-T
therapy or has had previous treatment with Iber.
6. 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.
7. 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.
8. Is pregnant or breast feeding.
9. Has clinically significant cardiovascular disease including, albeit not limited to:
1. Uncontrolled or any New York Heart Association Class 3 or 4 congestive heart
failure
2. Uncontrolled angina, history of myocardial infarction, unstable angina or
stroke within 6 months before study entry
3. Uncontrolled hypertension or clinically significant arrhythmias not controlled
by medication.
10. 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.
11. 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.
12. Has recent major surgery within 4 weeks or significant gastrointestinal (GI) disease
that would interfere with GI absorption of oral medications.
13. Has a condition, including autoimmune disease, requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days before study therapy administration.
Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone
equivalents are permitted in the absence of active autoimmune disease.
14. Has received treatment with allogeneic stem cell transplant within 6 months before
the first dose of study treatment and if > 6 months from allogeneic stem cell
transplantation (alloSCT) must be off all immunosuppression and without evidence of
active graft-versus-host disease (GVHD).
15. Uncontrolled epilepsy or new/recent seizure activity within 6 months of study entry.
16. Live vaccine administered within 4 weeks prior to study therapy.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Calfornia, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Contact:
Last name:
Kenya Gomez
Email:
Kenya.Gomez@ucsf.edu
Contact backup:
Phone:
877-827-3222
Email:
cancertrials@ucsf.edu
Start date:
July 1, 2024
Completion date:
June 30, 2028
Lead sponsor:
Agency:
Thomas Martin, MD
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Collaborator:
Agency:
Janssen Research & Development, LLC
Agency class:
Industry
Source:
University of California, San Francisco
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06348108
