Clinical trial NCT05972135: Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma
Official title: Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Teclistamab (TECVAYLI™)
Humanized IgG-4 PAA bispecific antibody
CD3 receptor complex
RRMM-Relapsed or Refractory Multiple Myeloma
MM-Multiple Myeloma
Tocilizumab prophylaxis
CRS- Cytokine Release Syndrome
Neurologic toxicity
ICANS-Immune Effector Cell-associated Neurotoxicity Syndrome
Talquetamab (TALVEY™)
GPRC5D
BCMA
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Johnson & Johnson
First posted: 2023-08-02
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase II study to evaluate the outpatient administration of Teclistamab or Talquetamab in Multiple Myeloma patients

Detailed description: * This is a two-arm, non-randomized, multicenter, prospective study in adult patients with RRMM, who are administered Teclistamab (TECVAYLI™) or Talquetamab (TALVEY™), in the post-marketing setting.
* Teclistamab (TECVAYLI™) is a humanized IgG-4 PAA bispecific antibody designed to target the CD3 receptor complex on T cells and BCMA on B-lineage cells.
* Talquetamab (TALVEY™) is a humanized IgG-4 bispecific antibody designed to target the CD3 receptor complex on T cells and GPRC5D-expressing multiple myeloma (MM) cells This study will investigate the use of prophylactic tocilizumab to reduce the incidence and severity of CRS associated with teclistamab or talquetamab administration, to enable administration of the step-up dosing regimen of teclistamab or talquetamab in an outpatient setting.

Eligibility criteria: Inclusion Criteria:

* Be ≥18 years of age (or the higher legal age in the jurisdiction in which the study is taking place) at the time of informed consent
* Has documented diagnosis of MM according to the IMWG diagnostic criteria (Rajkumar 2011).
* Has received 2 or more prior MM therapies including a PI, IMiD and CD38 antibody.
* Has an ECOG performance status (Oken 1982) of 0 to 1.
* Measurable disease at screening, as assessed by local laboratory, defined by any of the following:

  * Serum M-protein level ≥0.5 g/dL; or
  * Urine M-protein level ≥200 mg/24 hours; or
  * Light chain MM without measurable M-protein in the serum or the urine: serum free light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
  * For participants without measurable disease in the serum, urine, or involved FLC, presence of plasmacytomas (≥2 cm).
* Human immunodeficiency virus-positive participants are eligible if they meet all of the following:

  * No detectable viral load (i.e., \<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 highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to enrollment. A change in HAART due to toxicity is allowed up to 4 weeks prior to enrollment.
* Adequate organ system function
* Body weight \>35 kg.
* A participant of childbearing potential must have a negative highly sensitive serum (β-hCG) at screening and within 72 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
* A participant must agree to abide by protocol defined contraceptive requirements for the duration of the study
* A participant must sign an ICF indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
* A participant is required to stay within 30 minutes of transportation to the site and remain in the company of a competent adult at all times until 48 hours following administration of all doses within the teclistamab or talquetamab step-up dosing schedule
* A participant must agree to carry the study participant identification wallet card at all times.
* A participant must comply with all the protocol requirement procedures, including measuring and recording of body temperature and blood oxygen saturation twice daily (≥8 hours apart) during the first 2 cycles of teclistamab or talquetamab treatment and coming to the study site for safety assessments.
* A participant and the accompanying competent adult must be made aware of the presenting sign sand symptoms of teclistamab- or talquetamab- associated toxicities, including but not limited to CRS, ICANS, infections, etc. The accompanying competent adult must watch the participant at all times for teclistamab- or talquetamab- associated toxicities, until 48 hours after the first treatment dose of teclistamab or talquetamab.

Exclusion Criteria:

* Has a rapidly progressing disease per investigator assessment.
* Has plasma cell leukemia (\>2.0×10\^9/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis.
* Has known active CNS involvement or exhibits clinical signs of meningeal involvement of MM.
* Has risk factors for developing clinically significant TLS and requiring management with increased hydration, allopurinol, or rasburicase.
* Has myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 12 months) other than RRMM. The only allowed exceptions are:

  * Any malignancy that was not progressing nor requiring treatment change in the last 12 months.
  * Malignancies treated within the last 12 months and considered at very low risk for recurrence:
  * Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, \<3 cm, no CIS).
  * Skin cancer (non-melanoma or melanoma).
  * Noninvasive cervical cancer.
  * Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents.
  * Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment).
  * Other malignancy that is considered at minimal risk of recurrence.
* Has Grade ≥3 hematologic AEs or Grade ≥3, clinically significant non-hematologic AEs.
* Has fever or active infection (bacterial, viral, or uncontrolled systemic fungal) at time of study enrollment.
* Has active autoimmune disease or a documented history of autoimmune disease with the exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing.
* Has clinically significant coagulopathy that would increase the risk of bleeding in the setting of cytopenia.
* Shows a deterioration in neurologic status, including mental status changes such as confusion or increased somnolence.
* Has psychiatric disorders (eg, alcohol or drug abuse), dementia, or altered mental status that would compromise the ability to provide informed consent or comply with the clinical protocol.
* History of stroke, transient ischemic attack or seizure within 6 months of signing ICF.
* Presence of the following cardiac conditions:

  * New York Heart Association stage III or IV congestive heart failure.
  * Myocardial infarction or CABG ≤6 months prior to enrollment.
  * History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
  * History of severe non-ischemic cardiomyopathy.
  * Poorly controlled coronary artery disease and/or congestive heart failure.
  * Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
* Has 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.
* Has 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 12 weeks following the completion of therapy, the participant is eligible for the study.
* Has COPD with FEV1 \<50% of predicted.
* Has eGFR \<20 ml/min or is dependent on dialysis.
* Has other medical 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 (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
* For talquetamab arm only: Prior Grade 3 or higher CRS related to any T-cell redirection (e.g., CD-3 redirection technology or CAR-T cell therapy), or any prior GPRC5D-targeting therapy.
* Has received packed RBC or platelet transfusions within the last 7 days prior to dosing.
* Has contraindications to the use of tocilizumab or IVIG per local prescribing information.
* Has received live vaccine(s) within 1 month prior to screening or plans to receive live vaccines during the study.
* Has received live, attenuated vaccine within 30 days before the first dose of teclistamab or talquetamab. Live, attenuated influenza vaccines are permitted as late as 30 days before the study treatment.
* Has received an investigational intervention or used an invasive investigational medical device within 14 days before the planned first dose of study treatment or received an investigational biological product within 14 days or 5 half-lives, whichever is longer, before the planned study treatment, or is currently enrolled in an investigational study.
* History of antitumor therapy as follows, before the first dose of study drug:

  * Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.
  * Monoclonal antibody treatment for MM within 21 days.
  * Cytotoxic therapy within 21 days.
  * PI therapy within 14 days.
  * Immunomodulatory agent therapy within 7 days.
  * For teclistamab arm only: Prior Ggene modified adoptive cell therapy (eg, chimeric antigen receptor modified \[CAR\]-T cells, NK cells) within 3 months. or BCMA therapy).
  * Radiotherapy within 14 days or focal radiation within 7 days.
  * For teclistamab arm only: Prior gene modified adoptive cell therapy
  * For talquetamab arm only: Prior CAR-T or BCMAbispecific antibody therapy are allowed.
* History of stem cell transplant:

  * An allogeneic stem cell transplant within 6 months. Participants who received an allogeneic transplant must be off all immunosuppressive medications for ≥42 days without signs of graft-versus-host disease.
  * An autologous stem cell transplant ≤12 weeks before the first dose of study drug.

Primary outcomes:
measure: Incidence of CRS of any grade during the first two cycles
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Incidence of recurrent CRS of any grade
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
measure: Incidence of CRS of any grade
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Incidence of recurrent CRS of any grade
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Incidence of Grade ≥2 CRS
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
measure: Incidence of Recurrent Grade ≥2 CRS
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
measure: Incidence of Grade ≥2 CRS
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Incidence of Recurrent Grade ≥2 CRS
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Incidence of Grade ≥3 and any grade infections
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Incidence of All grade and Grade ≥3 neurotoxicity
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
measure: Incidence of All grade and Grade ≥3 ICANS
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
measure: Incidence of All grade neutropenia and Grade ≥3 neutropenia
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Incidence of all grade febrile neutropenia and Grade ≥3 febrile neutropenia
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Total length of each hospital stay
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Number of hospitalizations per participant
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Healthcare resource utilization in the outpatient setting
timeFrame: From first dose of teclistamab or talquetamab, from Day 1 first step-up dose to the end of Cycle 2 (each cycle is 28 days)
measure: Overall response rate (ORR)
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Time to initial response (TTR)
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Time to best response (TTBR)
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Duration of response (DOR)
timeFrame: Day 1 of every 2 cycles From Cycle 1 Day 1 and up to approximately 12 months of teclistamab treatment or 6 months for talquetamab. (each cycle is 28 days)
measure: Time to next treatment (TTNT)
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Overall survival (OS)
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Progression-free survival (PFS)
timeFrame: Day 1 of every 2 cycles From Cycle 1 Day 1 and up to approximately 12 months of teclistamab or 6 months for talquetamab treatment. (each cycle is 28 days)_
measure: Timing of each hospital stay
timeFrame: Up to 12 months of teclistamab or 6 months for talquetamab treatment
measure: Talquetamab Arm only: Number of participants who have had a change in health-related quality of life parameters, from baseline to end of treatment
timeFrame: Up to 6 months for talquetamab treatment
measure: Talquetamab Arm only: Number of participants with oral toxicities
timeFrame: Up to 6 months for talquetamab treatment
measure: Talquetamab Arm only: Number of patients with overall side effects
timeFrame: Up to 6 months for talquetamab treatment
measure: Talquetamab Arm only: Rate of treatment-emergent dysgeusia, oral mucositis, dysphagia, and xerostomia
timeFrame: Up to 6 months for talquetamab treatment
measure: Talquetamab Arm only: Time to first onset of treatment-emergent dysgeusia, oral mucositis, dysphagia, and xerostomia
timeFrame: Up 6 to months for talquetamab treatment
measure: Talquetamab Arm only: Duration of treatment-emergent dysgeusia, oral mucositis, dysphagia, and xerostomia
timeFrame: Up 6 to months for talquetamab treatment
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Columbia
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Nashville
country: United States
facility: TriStar Bone Marrow Transplant
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Center
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Robert Rifkin, MD
role: STUDY_CHAIR
References: