A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects with Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma10018865
- Registration Number
- NL-OMON54560
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
1.>=18 years of age.
2.Documented initial diagnosis of multiple myeloma according to IMWG diagnostic
criteria (attachment 8 of the protocol)
3. Part 1: Subjects with measurable multiple myeloma who have progressed on, or
could not tolerate, all available established therapies.
Part 2: Subjects with multiple myeloma measurable by central laboratory
assessment who have progressed on, or could not tolerate, all available
established therapies. If central laboratory assessments are not available,
relevant local laboratory measurements must exceed the minimum required level
by at least 25%.
Part 3: Measurable disease: Cohort A, Cohort B, and Cohort C: Multiple myeloma
must be measurable by central laboratory assessment. If central laboratory
assessments are not available, relevant local laboratory
measurements must exceed the minimum required level by at least 25%. Cohort A
and Cohort C: have previously received >=3 prior lines of therapy that included
at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have not
been exposed to T cell redirection therapies such as CAR-T or bispecific
antibodies. Cohort B: have previously received >=3 prior lines of therapy that
included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and
have been exposed to T cell redirection therapies such as CAR-T or bispecific
antibodies.
4.Eastern Cooperative Oncology Group (ECOG) performance status score, of 0 or 1
for part 1 and 2 and 0-3 for part 3
5. Pretreatment clinical laboratory values meeting the predefined criteria,
during the Screening Phase (see table on pg 120 of protocol)
6. Women of childbearing potential (WOCBP) must have a negative pregnancy test
at screening and prior to the first dose of study drug using a highly sensitive
pregnancy test either serum (β human chorionic gonadotropin [β-hCG]) or urine.
(a woman is considered of childbearing potential (WOCBP) ie, fertile, following
menarche and until becoming post-menopausal unless permanently
sterile. Permanent sterilization methods include hysterectomy, bilateral
salpingectomy and bilateral oophorectomy.),
7.Women:
Women must be (as defined in Attachment 16) either one of the following:
a) Not of childbearing potential
b) Of childbearing potential and
- Practicing true abstinence OR
- Have a sole partner who is vasectomized OR
- Practicing at least 1 highy effective user-independent method of
contraception (see Attachment 16)
Subject must agree to continue to above from the time of signing the informed
consent form (ICF), while receiving study drug, and until 100 days after the
last dose of study drug. Women of childbearing potential must agree to
pregnancy testing (serum or urine) within 100 days after the last study drug
administration.
Men
Men must wear a condom (with or without spermicidal foam/gel/cream/suppository)
when engaging in any activity that allows for passage of ejaculate to another
person, during the study and for 100 days after the last dose of study drug.
His female partner, if of childbearing potential, must also be practicing a
highly effective methdod of contraception (see Attachment 16).
If the male subject is vasectomized, he still must wear a condom (with or
without spermicidal foam/gel/cream/suppository) but his female partner is not
required
1. 1. Prior Grade 3 or higher CRS related to any T cell redirection (eg, CD-3
redirection technology or CAR-T cell therapy) or any prior GPRC5D targeting
therapy.
2. Prior antitumor therapy as follows, prior to the first dose of study drug:,
• Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified
T cells, natural killer [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., •Monoclonal antibody treatment for multiple
myeloma within 21 days.,
• Cytotoxic therapy within 21 days., • Proteasome inhibitor therapy within 14
days.,
• Immunomodulatory agent therapy within 7 days.
• Radiotherapy within 14 days. However, if palliative focal radiation is used,
the subject is eligible irrespective of, the end date of radiotherapy.,
• Part 3 only:
o Cohort A and cohort C: exposed to a CAR-T or T cell redirection therapy at
any time.
o Cohort B: T cell redirection therapy within 3 months
3. Participants who received or plan to receive any live, attenuated
vaccine within 4 weeks prior to the first dose, during treatment, or
within 4 weeks of the last dose of talquetamab. Non-live or nonreplicating
vaccines approved or authorized for emergency use (eg,COVID-19) by local health
authorities are allowed.
4. Toxicities from previous anticancer therapies should have resolved to,
baseline levels or to Grade 1 or less except for alopecia or peripheral,
neuropathy.,
5. Received a cumulative dose of corticosteroids equivalent to >=140 mg of
prednisone within the 14-day period before the first dose of study, drug.,
6. Received either of the following:
-An allogenic stem cell transplant within 6 months before first dose of study
drug. Subjects who received an allogeneic transplant must be off all
immunosuppressive medications for 6 weeks without signs of GVHD.:
-An autologous stem cell transplant <=12 weeks before first dose of study drug,
7.Central nervous system (CNS) involvement or clinical signs of meningeal
involvement of multiple myeloma. If either is suspected, negative whole brain
magnetic resonance imaging (MRI) and lumbar cytology are required. ,
8. Plasma cell leukemia (>2.0 x 10 to the 9th/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 (AL) amyloidosis.,
9. Known to be seropositive for human immunodeficiency virus or, acquired
immune deficiency syndrome.,
10. Hepatitis B infection as defined according to the American Society of,
Clinical Oncology guidelines. In the event the infection status is unclear,,
quantitative levels are necessary to determine the infection status., Active
Hepatitis C infection as measured by positive HCV-RNA testing., Subjects with a
history of Hepatitis C virus antibody positivity must, undergo HCV-RNA
testing.,
11. Pulmonary compromise requiring supplemental oxygen use to, maintain
adequate oxygenation.,
12. Known allergies, hypersensitivity, or intolerance to talquetamab or, its
excipients.,
13. Any serious underlying medical condition, such as:, • Evidence of serious <b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* Part 1 (Dose Escalation): Frequency and type of dose-limiting toxicity (DLT),<br /><br>and frequency and severity of adverse events, serious adverse<br /><br>events, and laboratory abnormalities<br /><br>* Part 2 (Dose Expansion): Frequency and severity of adverse events, serious<br /><br>adverse events, and laboratory abnormalities<br /><br>* Part 3: Overall Response Rate (partial response or better) as defined by the<br /><br>IMWG criteria based on review by the Independent Review Committee.</p><br>
- Secondary Outcome Measures
Name Time Method