Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)

NCT06993675 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000038510
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Multiple myeloma is characterized by a pattern of recurrent relapse and remains an incurable malignancy. Participants with minimal residual disease (MRD) after front line therapy with induction and transplant have worse prognosis than those with MRD negative disease. Bispecific T-cell-based immunotherapies have the potential to promote further reduction of malignant plasma cells thus improving rates of MRD negativity and improve patient outcomes. In this study, participants who are MRD positive after front line therapy will receive consolidation with GPRC5D-targeted bispecific talquetamab. We will test MRD negative conversion and if MRD negativity was not achieved, the participant will switch to a different target using the B-cell maturation antigen TCE, teclistamab. Consolidation will be continued for up to 1 year in participants who have achieved MRD negativity. After consolidation therapy on this protocol is complete, participants may continue to be treated with standardof- care (SOC) maintenance therapy.

Conditions

Multiple Myeloma

Keywords

minimal residual disease; ROTATE

Outcome Measures

Primary Outcomes (1)

• Rate of MRD Negative Response at 10^-5 Sensitivity Using NGS ClonoSEQ Assay in Participants with Newly Diagnosed Multiple Myeloma Treated with Talquetamab Consolidation With or Without Sequential Teclistamab by 12 Months

  The primary outcome measure will evaluate the efficacy of talquetamab consolidation therapy, with or without the sequential use of teclistamab, by assessing the rate of minimal residual disease (MRD) negative response at a sensitivity level of 10\^-5. This evaluation will be conducted using the next-generation sequencing (NGS) ClonoSEQ assay. The primary endpoint is the proportion of participants who achieve MRD negativity at 10\^-5 sensitivity after consolidation therapy with talquetamab, with or without the sequential use of teclistamab, by 12 months from the start of treatment. MRD negative response is defined as the absence of detectable myeloma cells in bone marrow, as determined by the highly sensitive NGS ClonoSEQ assay. This measure aims to determine the depth of response and the potential of the treatment regimen to achieve sustained deep remission in participants with newly diagnosed multiple myeloma.

  12 months from the start of treatment

Secondary Outcomes (5)

• Complete Response and MRD-Negative Complete Response in Multiple Myeloma Patients Treated with Talquetamab Consolidation, With or Without Sequential Teclistamab

  At baseline then at Cycle 7, each cycle is 28 days

• Assessment of Minimal Residual Disease (MRD) at 10^-6 Sensitivity in Multiple Myeloma Patients

  At baseline then at Cycle 7, each cycle is 28 days

• Determination of Sustained MRD-Negative Rate at One Year in Multiple Myeloma Patients

  One year post-treatment

• Quality of Life Assessment via Patient-Reported Outcomes in Response to Treatment

  Day 1 of Cycles 1-6, where each cycle is 28 days, then at EOT(treatment durations is 15-24 months) and Safety Follow-Up visits(patients will be followed for 6 months)

• Assessment of Treatment-Related Adverse Events in Multiple Myeloma Patients

  From baseline till the first safety follow-up visit; approximately 15-24 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Talquetamab is a GPRC5DxCD3 bispecific antibody. It is supplied as a sterile, preservative-free solution for subcutaneous administration. Teclistamab is a BCMAxCD3 bispecific antibody. It is supplied as a sterile, preservative-free solution for subcutaneous administration.

Drug: Talquetamab; Drug: Teclistamab

Interventions

Talquetamab DRUG

Talquetamab is a GPRC5DxCD3 bispecific antibody. It is supplied as a sterile, preservative-free solution for subcutaneous administration.

Arm 1

Teclistamab DRUG

Teclistamab is a BCMAxCD3 bispecific antibody. It is supplied as a sterile, preservative-free solution for subcutaneous administration.

Arm 1

Eligibility Criteria

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

You may qualify if:

• To qualify for participation in this study, an individual must satisfy each of the following criteria:
• Provision of signed and dated 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 HDM ASCT within 60-120 days. If consolidation with the same induction regimen is used post ASCT, enrolment up to 60 days post consolidation.
• Must have MRD positive disease at 10-5 based on NGS with a PR or better response.
• Must not be progressing as per 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 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. Adequate bone marrow function:
• Hemoglobin 8 g/dl (³5mmol/L; without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted).
• Absolute neutrophil count ≥1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated-G-CSF).
• Platelets ³75×109/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 (see https://www.mdcalc.com/calc/43/creatinine-clearance-cockcroft-gault-equation)
• Must have adequate liver function:
• Aspartate aminotransferase ≤2.5 folds of the upper limit of normal (ULN).
• Alanine aminotransferase ≤2.5 folds of the ULN.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Prior or concurrent exposure to any of the following within the specified timeframe before first dose of study drug:
• 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.
• PI therapy within 14 days.
• IMiD agent therapy within 14 days.
• Radiotherapy within 14 days or focal radiation within seven days.
• Gene-modified adoptive cell therapy (e.g., NK cells) within three months.
• Prior exposure to a bispecific T-cell engager or CAR T-cell therapy.
• An active or suspected infection at time of screening. For rescreening refer to section 5.5.
• 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 RNA for six months are eligible. Participants with no active hepatitis B infection (e.g., HBsAg negative, anti-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.

Sponsors & Collaborators

• Noffar Bar: lead
• Johnson & Johnson: collaborator

Study Sites (2)

Yale University

New Haven, Connecticut, 06519, United States

RECRUITING

Wilmot Cancer Center, Clinical Trial Office of the University of Rochester Medical Center

Rochester, New York, 14642, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

talquetamab

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Noffar Bar, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carole Ramm

CONTACT

203-785-5702; carole.ramm@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Hematology)

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: May 29, 2025
• Study Start: August 21, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)