A Multi-arm Phase 1b Study of Talquetamab With Other Anticancer Therapies in Participants with Multiple Myeloma

Recruiting

Conditions: Kahler's disease
Multiple Myeloma
10018865

Registration Number: NL-OMON53994

Lead Sponsor: Janssen-Cilag

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 14

Inclusion Criteria

1. Be >=18 years of age.
2. Sign an ICF indicating that the participant understands the purpose of, and
procedures required for, the study and is willing to participate in the study,
including the requirement to provide information during the Posttreatment
Follow-up Period. Consent must be obtained prior to the initiation of any
study-related tests or procedures that are not part of standard of care for the
participant*s disease.
3. Have documented initial diagnosis of multiple myeloma according to IMWG
diagnostic criteria.
4. Meet treatment regimen-specific requirements as follows:
a. Treatment Regimen A (talquetamab + carfilzomib): Participants with multiple
myeloma who have received >=3 prior lines of therapy, including a PI, an IMiD,
and an anti-CD38 mAb
b. Treatment Regimen B (talquetamab + daratumumab + carfilzomib): Participants
with multiple myeloma who have received >=3 prior lines of therapy, including a
PI and an IMiD
c. Treatment Regimen C (talquetamab + lenalidomide): Participants with multiple
myeloma who have received >=1 prior lines of therapy,
including a PI and an IMiD
d. Treatment Regimen D (talquetamab + daratumumab + lenalidomide):
o Participants with >=1 prior lines, including a PI and an IMiD.
o Participants who are lenalidomide naïve or have newly diagnosed disease. Any
newly diagnosed participants must be transplant ineligible. Where local
treatment guidelines allow, newly diagnosed transplant-eligible participants
who chose to defer ASCT as initial therapy may also be enrolled.
e. Treatment Regimen E (talquetamab + pomalidomide): Participants with multiple
myeloma who have received >=2 prior lines of therapy, including a PI and
lenalidomide
5. Have measurable disease at screening as defined by at least 1 of the
following:
a. Serum M-protein level >=1.0 g/dL; or
b. Urine M-protein level >=200 mg/24 hours; or
c. Light chain multiple myeloma: Serum Ig FLC >=10 mg/dL and abnormal serum Ig
kappa lambda FLC ratio.
6. Have an ECOG performance status score of 0 or 1 at screening and immediately
before the start of study treatment administration.
7. Have clinical laboratory values meeting the following criteria during the
Screening Period:
Hemoglobin 8.0 g/dL ( 5 mmol/L) (without prior RBC transfusion within 7 days
before the laboratory test; recombinant human erythropoietin use is permitted)
Platelets 50×109/L (without transfusion support in the 7 days prior to the
laboratory test)
ANC 1.0×109/L (prior growth factor support is permitted but must be without
support for 7 days if received G-CSF or GM-CSF or 14 days if received peg-G-CSF)
AST and ALT <=2.5×ULN
Creatinine clearance 30 mL/min based upon Modified Diet in Renal Disease
formula calculation (Appendix 7) or a 24-hour urine collection.
Total bilirubin <=1.5×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)
8. A woman of childbearing potential must have a negative highly sensitive
serum (β-hCG) pregnancy test at screening and a negative urine or serum
pregnancy test within 24 hours before the start of study treatment
administration.
9. A woman must be:
a. Not of

Exclusion Criteria

Any potential participant who meets any of the following criteria will be
excluded from participating in the study:
1. Prior treatment with any therapy that targets GPRC5D.
2. Prior antitumor therapy as follows, in the specified time frame prior to the
first dose of study treatment:
a. 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.
b. Gene-modified adoptive cell therapy (eg, CAR modified T-cells, NK cells)
within 3 months.
c. mAb treatment or bispecific T-cell redirector therapy for multiple myeloma
within 21 days.
d. Cytotoxic therapy within 21 days.
e. PI therapy within 14 days.
f. Immunomodulatory agent therapy within 7 days.
g. Radiotherapy within 14 days. However, if palliative focal radiation is used,
the participant is eligible irrespective of the end date of radiotherapy.
3. Live, attenuated vaccine within 4 weeks before the first dose of study
treatment.
4. Non-hematologic toxicity from prior anticancer therapy that has not resolved
to baseline levels or to Grade <=1 (except alopecia [any grade] or peripheral
neuropathy Grade <=3).
5. Received a cumulative dose of corticosteroids equivalent to >=140 mg of
prednisone within the 14-day period before the start of study treatment
administration
6. 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.
7. Active CNS involvement or exhibition of clinical signs of meningeal
involvement of multiple
8. Active plasma cell leukemia (>2.0×109/L plasma cells by standard
differential), Waldenstro*m*s macroglobulinemia, POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or
primary amyloid light chain amyloidosis.
9. Known to be seropositive for human immunodeficiency virus.
10. Seropositive for HBV, defined by a positive test for HbsAg. Participants
with resolved infection (ie, participants who are HbsAg negative but positive
for hepatitis B core antibody[anti-HBc] and/or positive for hepatitis B surface
antibody [anti-HBs]) must be screened using real-time PCR measurement of HBV
DNA levels. Those who are PCR positive will be excluded. EXCEPTION:
Participants with serologic findings suggestive of HBV vaccination (anti-HBs
positivity as the only serologic marker) and a known history of prior HBV
vaccination do not need to be tested for HBV DNA by PCR.
11. Active hepatitis C infection as measured by positive HCV-RNA testing.
Participants with a history of HCV antibody positivity must undergo HCV-RNA
testing.
12. Known allergies, hypersensitivity, or intolerance to any study treatment or
their excipients
13. Any serious underlying medical condition, such as:
a. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal
infection.
b. Active autoimmune disease requiring systemic immunosuppressive therapy
within 6 months before start of study treatment.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Number of Participants with Adverse Events (AEs) as a Measure of Safety and<br /><br>Tolerability<br /><br>- Number of Participants with AEs by Severity<br /><br>- Number of Participants with Clinically Significant Abnormalities in<br /><br>Laboratory Parameters<br /><br>- Number of Participants with Dose Limiting Toxicity (DLT)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Overall Response Rate (ORR)<br /><br>- Very Good Partial Response (VGPR) or Better Response Rate<br /><br>- Complete Response (CR) or Better Response Rate<br /><br>- Stringent Complete Response (sCR)<br /><br>- Duration of Response<br /><br>- Time to Response<br /><br>- Serum Concentration of Talquetamab<br /><br>- Serum Concentration of Daratumumab<br /><br>- Number of Participants with Anti-Drug Antibodies to Talquetamab<br /><br>- Number of Participants with Anti-Drug Antibodies to Daratumumab<br /><br>- Number of Participants with Anti-Drug Antibodies to Recombinant Human<br /><br>Hyaluronidase PH20 Enzyme (rHuPH20)</p><br>