Talquetamab treatment for elderly patients with early relapse multiple myeloma

A Phase 2 Single-Arm Study of Subcutaneous Talquetamab in Elderly Patients With Multiple Myeloma in Early Relapse

This study is testing if a new treatment called Talquetamab can help older patients with early relapse multiple myeloma who can't tolerate stronger therapies feel better and have a safer option.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 70 Years and up
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (Academic / other)
• Drugs / interventions: talquetamab, daratumumab, chimeric antigen receptor, radiation, prednisone, CAR T
• Locations: 1 site (New York, New York)
• Trial ID: NCT06827860 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of Talquetamab, a bispecific antibody, in elderly patients suffering from early relapse of multiple myeloma. The study focuses on patients who have become refractory to multiple standard therapies and are not suitable for aggressive treatments like stem cell transplantation. By redirecting T cells to target myeloma cells, the trial aims to provide a more tolerable treatment option for this vulnerable population. The trial will assess the efficacy and safety of Talquetamab in combination with Daratumumab.

Who should consider this trial

Good fit: Ideal candidates for this study are elderly patients diagnosed with multiple myeloma who have experienced early relapse after one to three prior therapies.

Not a fit: Patients who are not experiencing early relapse or those who have not been previously treated for multiple myeloma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new, effective option for elderly patients with limited treatment choices due to early relapse of multiple myeloma.

How similar studies have performed: Other studies have shown promising results with bispecific antibodies in treating multiple myeloma, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

* Documented multiple myeloma as defined by the criteria below:

  * Multiple myeloma diagnosis according to the IMWG diagnostic criteria
  * Measurable disease at screening as assessed by central laboratory, defined by at least 1 of the following:
* Serum M-protein level ≥0.5 g/dL (central laboratory)
* Urine M-protein level ≥200 mg/24 hours (central laboratory)
* Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain ≥10 mg/dL or \>100 mg/L (central laboratory) provided the serum free light chain ratio is abnormal (0.22 to 1.52 \[central laboratory\])

NOTE: Local laboratory results of blood and urine M-protein measurements may be used to determine initial eligibility. Central laboratory results should still be obtained prior to the start of administration of study treatment in order to establish baseline values and confirm the results from the local laboratory.

• Relapsed or refractory disease as defined below:

* Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease by IMWG criteria \>60 days after cessation of treatment.
* Refractory disease is defined as \<25% reduction in M-protein or confirmed progressive disease by IMWG criteria during previous treatment or ≤60 days after cessation of treatment. Received at least 1 prior line(s) of antimyeloma therapy including a minimum of 2 consecutive cycles

NOTE: Participant must have undergone ≥1 complete cycle of treatment for each regimen, unless progressive disease was the best response to the regimen.

NOTE: A single line of therapy may consist of 1 or more agents and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy.

* Subject must have received at least ≥2 prior line(s) of systemic antimyeloma therapy of treating physician's discretion, including a PI and an IMID
* Subjects who are anti-CD38 monoclonal antibody-naïve, exposed, or refractory will be allowed in Part 1; Only subjects who are anti-CD38 antibody-naïve or exposed will be allowed in Part 2, whereas subjects refractory to anti-CD38 monoclonal antibody will not be allowed in Part 2
* Have clinical laboratory values meeting the following criteria during the Screening Phase: Hematology Hemoglobin: ≥7 g/dL (≥4.96 mmol/L; without transfusion support or erythropoietin use within 7 days before the laboratory test) Platelets: ≥50×109/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) 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 GCSF before the laboratory test) Chemistry AST and ALT: ≤2.5×ULN eGFR: ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation Total bilirubin: ≤2.0×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required) Serum calcium corrected for albumin: ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L;)
* Human immunodeficiency virus-positive participants are eligible if they meet all of the following:

  * No detectable viral load (ie, \<50 copies/mL) at screening
  * CD4+ count \>300 cells/mm3 at screening
  * No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening
  * Receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.

Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment) • A male participant must agree to wear a condom (with spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 100 days after receiving the last dose of study treatment.

NOTE: If the male participant is vasectomized, he still must wear a condom (with foam/gel/film/cream/suppository), but his female partner is not required to use contraception.

* A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 100 days after receiving the last dose of study treatment.
* Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol (Section 2, including to not donate blood or blood components during the study and for 100 days after the last dose of study drug)
* Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the subject's disease.

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from participating in the study:

* Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the talquetamab and daratumumab Investigator's Brochure and appropriate prescribing information).
* Prior treatment with T-cell-engaging antibodies
* Prior antitumor therapy as follows, prior to the first dose of study drug:

  o Any prior GPRC5D-directed therapy
  * Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
  * Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.
  * Investigational vaccine other than SARS CoV-2 vaccine approved/ in use under emergency approval within 4 weeks o Live, attenuated vaccine within 4 weeks
  * Monoclonal antibody treatment for multiple myeloma within 21 days.
  * Cytotoxic therapy within 21 days.
  * Proteasome inhibitor therapy within 14 days. o Immunomodulatory agent therapy within 14 days. o Radiotherapy within 14 days or focal radiation within 7 days
* Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
* Received a maximum cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug.
* Stem cell transplantation:

  * Previous allogenic stem cell transplant
  * Received an autologous stem cell transplant ≤12 weeks before the first dose of study drug
* Known active CNS involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
* Plasma cell leukemia (\>20% circulating plasma cells and/or \>2.0 x 109/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M-protein\], and skin changes), or primary amyloid light chain amyloidosis.
* Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. The only allowed exceptions are:

  o Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured

  o Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
  * Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
  * Localized prostate cancer (N0M0):

    \- With a Gleason score of ≤6, treated within the last 24 months, or untreated and under surveillance
    * With a Gleason score of 3+4 that has been treated \>6 months prior to full study screening and considered to have a very low risk of recurrence, or
    * History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence
  * Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
  * Other malignancy that is considered cured with minimal risk of recurrence.
* Stroke or seizure within 6 months prior to signing ICF.
* Any of the following:

  * Active Hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status see Section Hepatitis B Virus Testing 8.7.1.18.7.1 for further required assessments.
  * Active hepatitis C infection as measured by positive HCV-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA for at least 12 weeks following the completion of therapy, the participant is eligible for the study.
* Any 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:

  * Uncontrolled diabetes o Acute diffuse infiltrative pulmonary disease
  * Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy within 7 days of start of study treatment
  * Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment.

EXCEPTION: Participants with vitiligo, controlled type I diabetes, and prior autoimmune thyroiditis 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 non-compliance with recommended medical treatments • Plans to father a child while enrolled in this study or within 100 days after the last dose of study drug.

  • Presence of the following cardiac conditions:
* New York Heart Association stage III or IV congestive heart failure
* Myocardial infarction or coronary artery bypass graft ≤6 months prior to randomization
* Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration o History of severe non-ischemic cardiomyopathy • Major surgery within 2 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 2 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 • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal of DLCO \<50%).

Note: FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 \<50% of predicted normal.

• Known moderate of persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification.

Note: Participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study.

NOTE: Investigators should ensure that all study inclusion/exclusion criteria have been met at screening and prior to the first dose of study drug. If a subject's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study drug is given such that he or she no longer meets all eligibility criteria, supportive treatment may be administered according to local standards of care, if necessary, so that eligibility criteria may be met and laboratory test(s) may be repeated once, to determine if the subject qualifies for the study. If inclusion/exclusion criteria are not met after further evaluation, the subject should be excluded from participation in the study.

Where this trial is running

New York, New York

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Larysa Sanchez, MD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Nicole K DeVito, BSc

Conditions Multiple Myeloma in Relapse; Talquetemab; Elderly patients; Early relapse; Multiple Myeloma