A Randomized Study Comparing Talquetamab in Combination WithDaratumumab and Pomalidomide or Talquetamab in Combination WithDaratumumab Versus Daratumumab, Pomalidomide and Dexamethasone, in Participants With Relapsed or Refractory Multiple Myeloma who Have Received at Least 1 Prior Line of Therapy
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-000202-22-DE
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 810
1. =18 years of age.
2. Documented multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b. Measurable disease at screening as defined by any of the following:
1) Serum M-protein level =0.5 g/dL (central laboratory); or
2) Urine M-protein level =200 mg/24 hours (central laboratory); or
3) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain =10 mg/dL (central laboratory), and abnormal serum immunoglobulin kappa lambda free light chain ratio (0.22 to 1.52 [central laboratory]).
3. Relapsed or refractory disease as defined below:
a. 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.
b. 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.
4. Received at least 1 prior line of antimyeloma therapy including a PI and lenalidomide. Participants who have received only 1 prior line of antimyeloma therapy must be considered lenalidomide-refractory (ie, have demonstrated progressive disease by IMWG criteria on or within 60 days of completion of lenalidomide-containing regimen). Participants who have received =2 prior lines of antimyeloma therapy must be considered lenalidomide exposed.
5. Documented evidence of progressive disease based on investigator’s determination of response by the IMWG criteria on or after their last regimen.
6. Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment.
7. Have clinical laboratory values as defined in the protocol
8. 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 highly active antiretroviral therapy (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.
9. A female participant of childbearing potential must have a negative highly sensitive urine or serum (ß human chorionic gonadotropin [ß hCG]) pregnancy test at screening, within 24 hours prior to the start of study treatment, and must agree to further urine or serum pregnancy tests during the study and within 100 days after receiving the last dose of study treatment.
10. A female participant must be:
a. Not of childbearing potential, or
b. Of childbearing potential and
1) Practicing true abstinence; or
2) Have a sole partner who is bilaterally vasectomized; or
3) Practicing 2 effective methods of contraception (at least 1 highly-effective, method of contraception). For participants who are of childbearing potential, see protocol Section 6.12.3 for details regarding concomitant use of estrogen containing products and pomalidomide
11. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 100 days after the last
dose of study treatment. Female participants should consider preservation of eggs
1. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to study drug excipients (refer to the talquetamab and daratumumab IB and appropriate prescribing information).
2. Disease is considered refractory to an anti-CD38 monoclonal antibody as defined per IMWG consensus guidelines (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody).
3. Prior or concurrent exposure to any of the following, in the specified time frame prior to randomization:
a. GPRC5D-directed therapy
b. Received prior pomalidomide therapy
c. T cell redirection therapy (for example, antibody therapy or BiTE’s) within 3 months
d. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
e. 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
f. Investigational vaccine other than SARS CoV-2 vaccine approved/ in use under emergency approval within 4 weeks
g. Live, attenuated vaccine within 4 weeks
h. Monoclonal antibody therapy within 21 days
i. Cytotoxic therapy within 21 days
j. PI therapy within 14 days
k. IMiD agent therapy within 14 days
l. Radiotherapy within 14 days or focal radiation within 7 days
4. Received either of the following:
a. An allogeneic SCT within 6 months before the first dose of study treatment. Participants who received an allogeneic transplant must be off all immunosuppressive medications during the 6 weeks before the start of study treatment administration without signs of graft versus host disease
b. An autologous SCT within 12 weeks before the start of study treatment administration.
5. A maximum cumulative dose of corticosteroids to =140 mg of prednisone or equivalent within 14-day period before the first dose of study drug
6. 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.
7. Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or
primary amyloid light chain amyloidosis.
8. 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:
a. Non-muscle invasive bladder cancer (solitary Ta- Papillary Urothelial Neoplasm of Low Malignant Potential or low grade, <3 cm, no CIS) treated within the last 24 months that is considered completely cured
b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
c. Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
d. Localized prostate cancer (N0M0):
1) With a Gleason score of =6, treated within the last 24 months, or untreated and under surveillance
2) 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
e. History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence
f. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receivin
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of Tal-DP and Tal-D, respectively, with DPd;Secondary Objective: 1. To further compare the efficacy of Tal-DP and Tal- D, respectively, with DPd<br>2. To assess the safety profile of Tal-DP and Tal-D<br>3. To characterize the PK of talquetamab<br>4. To assess the immunogenicity of talquetamab and daratumumab<br>5. To assess changes in patient-reported outcomes (PROs) with Tal-DP, DPd, and Tal-D;Primary end point(s): Progression Free Survival;Timepoint(s) of evaluation of this end point: Subjects will have disease evaluation performed by the central laboratory Day 1 of every cycle until disease progression. This endpoint will be evaluated at interim analysis and primary analysis. The projected time frame is up to 4 years.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. <br>-Overall response (PR or better)<br>- VGPR or better<br>- CR or better<br>- Overall MRD negativity status<br>- OS<br>- PFS2<br>- TTNT<br>2. Incidence and severity of AEs<br>3. PK parameters using population PK approach<br>4. Presence of ADAs to talquetamab and daratumumab<br>5. <br>-Time to worsening in symptoms, functioning, and overall HRQoL<br>- Change from baseline in symptoms, functioning, and overall HRQoL;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated at interim analysis and primary analysis.