Talquetamab with or without Teclistamab for the Treatment of Newly Diagnosed Multiple Myeloma, ROTATE Trial
This phase II trial tests the effect of talquetamab followed by teclistamab, if necessary, in treating patients with newly diagnosed multiple myeloma that have been treated with induction therapy and an autologous transplant and still have signs of disease in the bone marrow (minimal residual disease [MRD]). Talquetamab binds to a protein called CD3, which is found on T cells (a type of white blood cell), and to a protein called GPRC5D, which is found on myeloma cells and some other types of cells. This may help the immune system kill cancer cells. Talquetamab is a type of bispecific T-cell engager. Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen, a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving talquetamab followed by teclistamab, if necessary, may reduce the amount of cancer left and improve long-term survival rates in patients with multiple myeloma after their initial treatment.
Inclusion Criteria
- Provision of signed and dated informed consent form (ICF)
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female aged 18 years or older
- Newly diagnosed multiple myeloma participants who are transplant eligible and have completed at least four cycles of quadruplet, anti-CD38 antibody-based induction and have received high dose melphalan (HDM) autologous stem cell transplantation (ASCT) within 60-120 days. If consolidation with the same induction regimen is used post ASCT, enrollment up to 60 days post consolidation
- Must have MRD positive disease at 10^-5 based on next generation sequencing (NGS) with a partial response (PR) or better response
- Must not be progressing as per International Myeloma Working Group (IMWG) criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status Scale of 0 or 1. ECOG 2 or 3 are eligible for the study if the ECOG performance status (PS) score is related to stable physical limitations (e.g., wheelchair-bound due to prior spinal cord injury) and not related to multiple myeloma or associated therapy
- Hemoglobin 8 g/dl (5mmol/L; without prior red blood cell [RBC] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted)
- Absolute neutrophil count ≥ 1.0 x 10^9/L (prior growth factor support is permitted but must be without support for 7 days for granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF] and for 14 days for pegylated-G-CSF)
- Platelets 75 x 10^9/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test)
- Estimated creatinine clearance ≥ 30 mL/min based on the Cockcroft-Gault equation
- Aspartate aminotransferase ≤ 2.5 folds of the upper limit of normal (ULN)
- Alanine aminotransferase ≤ 2.5 folds of the ULN
- Serum bilirubin ≤ 1.5 x ULN (except in participants with congenital bilirubinemia, such as Gilbert syndrome where must be < 5 x ULN)
- Participants must adhere to the following reproductive and contraceptive requirements while on study treatment and for the specified duration after the last dose of talquetamab or teclistamab: * For participants receiving talquetamab, these criteria apply for three months after the last dose * For participants receiving teclistamab, these criteria apply for five months for those assigned female at birth and three months for those assigned male at birth * General requirements: ** Participants must not be pregnant or breastfeeding ** Participants must not donate gametes (i.e., eggs or sperm) or freeze gametes for future use related to assisted reproduction * For participants of childbearing potential: ** Participant of childbearing potential is defined as an individual who is premenopausal and capable of becoming pregnant, including those using contraception, those who are single, or those with partners who have had a vasectomy ** A negative highly sensitive pregnancy test must be obtained at screening within 72 hours before the first dose of talquetamab (first study treatment), and participants must agree to further pregnancy tests throughout the study ** Participants must practice at least one highly effective method of contraception * For partners of participants: ** If the participant's partner is of childbearing potential, the partner must also practice a highly effective method of contraception while the participant is on study treatment and for three months after the last dose of talquetamab or the last dose of teclistamab, unless the participant is vasectomized * Highly effective methods of contraception include, but are not limited to: ** Combined hormonal contraception (estrogen and progestogen) that inhibits ovulation (oral, intravaginal, or transdermal) ** Progestogen-only hormonal contraception that inhibits ovulation (oral, injectable, or implantable) ** Intrauterine device (IUD) ** Intrauterine hormone-releasing system ** Bilateral tubal occlusion ** Sexual abstinence (the reliability of abstinence must be evaluated concerning the duration of the clinical study and the participant's lifestyle) ** A vasectomized partner (provided the partner is the sole sexual partner of the women of child bearing potential [WOCBP] study participant and that the vasectomized partner has received medical confirmation of the surgical success)
Exclusion Criteria
- Prior or concurrent exposure to any of the following within the specified timeframe prior to randomization: * Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥ 5 half-lives, whichever is less * Investigational vaccine within four weeks * Monoclonal antibody therapy within 21 days * Cytotoxic therapy within 14 days * Primary immunodeficiency (PI) therapy within 14 days * Immunomodulatory imide drug (IMiD) agent therapy within 14 days * Radiotherapy within 14 days or focal radiation within seven days * Gene-modified adoptive cell therapy (e.g., chimeric antigen receptor modified T-cells, natural killer [NK] cells) within three months * Prior exposure to a bispecific T-cell engager or chimeric antigen receptor (CAR) T-cell therapy
- An active or suspected infection at time of screening
- Known history or serologic evidence of human immunodeficiency virus (HIV) infection
- Known history, virologic, or serological evidence of hepatitis B or C virus (HBV/HCV) infection; participants who had HCV but have received an antiviral treatment and show no detectable HCV viral ribonucleic acid (RNA) for six months are eligible. Participants with no active hepatitis B infection (e.g., hepatitis B virus surface antigen [HBsAg] negative, anti-hepatitis B virus core antibody [HBcAb] positive) who are under adequate prophylaxis per local standard of care against HBV reactivation may be eligible
- Class III or IV congestive heart failure
- Presence of clinically relevant central nervous system (CNS) pathology
- Another active malignancy that requires treatment
- Pregnancy or lactation
- Known allergic reactions to components of talquetamab or teclistamab
- Received a cumulative dose of corticosteroids equivalent to ≥ 140 mg of prednisone within 14 days before first dose of study drug
- Received a live, attenuated vaccine within four weeks before the first dose of study drug
- Plasma cell leukemia, smoldering multiple myeloma, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal [M]-protein, and skin changes), or primary light chain amyloidosis
- Any active malignancy (i.e., progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured: * Non-muscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, < 3 cm, no carcinoma in situ [CIS]) * Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone * Non-invasive cervical cancer * Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer (anti-antihormonal therapy is permitted) * Localized prostate cancer (M0, N0) with a Gleason score ≤ 7a, treated locally only (radiopharmaceutical [RP]/radiation therapy [RT]/focal treatment) * Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor-investigator * NOTE: In the event of any questions, consult with the sponsor-investigator prior to enrolling a participant
- Stroke, transient ischemic attack or seizure within six months prior to enrollment
- Presence of the following cardiac conditions: a. New York Heart Association stage III or IV congestive heart failure b. Myocardial infarction, unstable angina, or coronary artery bypass graft ≤ 6 months prior to randomization c. History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d. Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities
- Major surgery within two weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within two weeks after administration of the last dose of study treatment * NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is a question whether a procedure is considered a major surgery, the investigator must consult with the appropriate sponsor representative and resolve any issues before enrolling a participant in the study
- Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study, such as: * Acute diffuse infiltrative pulmonary disease * Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy * Active autoimmune disease requiring systemic immunosuppressive therapy within six months before start of study treatment ** Exception: Participants with vitiligo, controlled type I diabetes, and prior autoimmune thyroid disease that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed. * Disabling psychiatric conditions (e.g., alcohol or drug abuse), severe dementia, or altered mental status * Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments * History of noncompliance with recommended medical treatments
Additional locations may be listed on ClinicalTrials.gov for NCT06993675.
Locations matching your search criteria
United States
Connecticut
New Haven
PRIMARY OBJECTIVE:
I. To evaluate the efficacy of talquetamab consolidation, with or without sequential use of teclistamab, in increasing the MRD negative response rate for participants with newly diagnosed multiple myeloma.
SECONDARY OBJECTIVES:
I. To determine the complete response (CR) or better and MRD negative CR of participants with multiple myeloma treated with talquetamab, with or without sequential teclistamab in consolidation.
II. To assess MRD at level of 10^-6.
III. To determine sustained MRD negative rate at one year.
IV. To assess quality of life (QOL) through patient reported outcomes (PROs) in response to treatment.
V. To assess treatment-related adverse events.
TERTIARY/EXPLORATORY OBJECTIVES:
I. Biomarkers of response.
II. Biomarkers of response using MRD analysis on peripheral blood.
III. Analysis of the functional properties and composition of tumor microenvironment (TME).
IV. Analysis of immune cell composition and function in the peripheral blood as baseline and in response to therapy with T-cell engager (TCE).
OUTLINE:
STEP 1: Patients receive talquetamab subcutaneously (SC) on days 1, 4, 7, and 14 of cycle 1 and on day 1 of remaining cycles. Cycles repeat every 2 weeks for 3 or 6 cycles in the absence of disease progression or unacceptable toxicity. After 3-6 cycles, patients that are MRD negative, cycles repeat every 4 weeks for up to 1 year from MRD negative result. Patients MRD positive after 3 cycles receive an additional 3 cycles, and those patients that are MRD positive after 6 cycles continue to Step 2.
STEP 2: Patients receive teclistamab SC on days 1, 4, 7, and 15 of cycle 1 then on day 1 of remaining cycles. Cycles repeat every 4 weeks for 3 or 6 cycles in the absence of disease progression or unacceptable toxicity. Patients MRD negative after 3 or 6 cycles, cycles continue for up to 1 year from MRD negative result. Patients MRD positive after 3 cycles, receive an additional 3 cycles and those MRD positive after 6 cycles stop treatment and enter follow-up phase.
Additionally, patients undergo urine and blood sample collection, positron emission tomography (PET)/computed tomography (CT), CT or magnetic resonance imaging (MRI), and bone marrow biopsy and aspiration throughout the study.
After completion of study treatment, patients are followed every 3 months for up to 6 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationYale University
Principal InvestigatorNoffar Bar
- Primary ID2000038510
- Secondary IDsNCI-2025-06749
- ClinicalTrials.gov IDNCT06993675