The main purpose of this study are to determine the recommended Phase 2 dose(s) (RP2D) route
of administration, schedule and the maximum tolerated dose (MTD) in Part 1 and to determine
the safety and tolerability of JNJ-67571244 at the RP2D regimen(s) and to evaluate the
preliminary clinical activity of JNJ-67571244 in Part 2.
This is first-in-human (FIH) Phase 1, open-label, multicenter, dose escalation study with
dose expansion to evaluate the safety, tolerability, and preliminary antitumor activity of
JNJ-67571244 in adult participants with relapsed or refractory acute myeloid leukemia (AML)
or high-risk or very high-risk myelodysplastic syndromes (MDS) who are ineligible for or have
exhausted standard therapeutic options. The study is divided into 3 periods: a Screening
Phase (within 28 days before the first dose of study drug), a Treatment Phase (first dose of
study drug until the last dose of study drug) and a Post-treatment Follow-up Phase (up to the
end of study participation or end of study). Duration of study is 2.3 years.
Inclusion Criteria:
- A diagnosis of:
a) Acute Myeloid Leukemia (AML) according to the World Health Organization 2008
criteria with relapsed or refractory disease and ineligible for or have exhausted
standard therapeutic options b) high-risk or very high-risk Myelodysplastic Syndrome
(MDS) according to International Prognostic Scoring System (IPSS-R) and relapsed or
refractory after at least 1 course of hypomethylating therapy and ineligible for or
have exhausted standard therapeutic options per investigator discretion should be
included
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- Women of childbearing potential 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 or urine beta human chorionic gonadotropin [beta-hCG])
- Chemistry laboratory parameters within the following range during screening:
a) aspartate transaminase (AST) and alanine aminotransferase (ALT) less than or equal
to (<=) 3* upper limit of normal (ULN), b) Total bilirubin <=1.5*ULN; participants
with congenital bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated
bilirubin is within normal range, c) Creatinine clearance calculated or measured
creatinine clearance greater than or equal to (>=) 30 milliliters per minute (mL/min)
- Before the first dose of study drug:
1. Women of childbearing potential and fertile men who are sexually active must
agree to use a highly effective method of contraception (less than [<] 1 percent
{%} year failure rate from the time of signing the informed consent form [ICF])
during the study and for 90 days after the last dose of study drug. Contraception
must be consistent with local regulations regarding the use of birth control
methods for participants participating in clinical trials. 1) Participant must
agree to practice a highly effective method of contraception (failure rate of <1%
per year when used consistently and correctly). Examples of highly effective
contraceptives include: a) user-independent methods: implantable progestogen-only
hormone contraception associated with inhibition of ovulation; intrauterine
device; intrauterine hormone-releasing system; vasectomized partner; b)
user-dependent methods: combined (estrogen- and progestogen-containing) hormonal
contraception associated with inhibition of ovulation: oral, intravaginal, and
transdermal; progestogen-only hormone contraception associated with inhibition of
ovulation: oral and injectable, c) In addition to the highly effective method of
contraception, a man: 1) Who is sexually active with a woman of childbearing
potential must agree to use a barrier method of contraception (for example,
condom with spermicidal foam/gel/film/cream/suppository), 2) Who is sexually
active with a woman who is pregnant must use a condom, c) Women and men must
agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study
and for 90 days after the last dose of study drug
Exclusion Criteria:
- Willing and able to undergo allogenic stem cell transplant <=6 months before the first
dose of study drug, has evidence of graft versus host disease, or requires
immunosuppressant therapy (exception: daily doses less than 10 milligram (mg)
prednisone or equivalent are allowed for adrenal replacement)
- For Part 1 only, prior treatment with CD33 targeting therapy targeting T-cell
redirection (for example, CD-3 redirection technology or chimeric antigen receptor
[CAR]-T-cell therapy)
- For Part 1 only, prior Grade 3 cytokine release syndrome (CRS) related to any T-cell
redirection (for example, CD-3 redirection technology or CAR-T cell therapy)
- Prior treatment with a checkpoint inhibitor such that the first dose of JNJ-67571244
would occur within less than 5 half-lives. Prior treatment with chemotherapy, targeted
therapy, immunotherapy, radiotherapy, or treatment with an investigational anticancer
agent, an investigational drug (including investigational vaccines), within 2 weeks
prior to the first dose or at least 4 half-lives, whichever is less, or currently
receiving investigational therapy in a clinical trial. Hydroxyurea may be used
- Toxicities (except for alopecia, peripheral neuropathy, thrombocytopenia) from
previous anticancer therapies that have not resolved to baseline levels or to Grade 1
or less
