IRB Study Number 25-682
Status Recruiting
Phase Phase 2
Institute Taussig Cancer Institute
Description
Primary Objective:
• To evaluate the efficacy of JNJ-79635322
Secondary Objective:
• To further understand the efficacy of JNJ-79635322
• To evaluate and characterize the overall safety profile of JNJ-79635322
• To assess participants’ symptoms, functioning and HRQoL through PROs
• To characterize the PK of JNJ-79635322
• To assess the immunogenicity of JNJ-79635322
Exploratory Objective:
• To evaluate and explore the relationship between PK, AEs, and clinical response in patients treated wiJNJ-79635322
• To explore the relationship between MRD negativity and reduction in peripheral residual disease with duration and depth of clinical response in participants treated with JNJ-79635322
• To assess participants’ tolerability of JNJ-79635322 through PROs
Inclusion Criteria
Age
At the time of informed consent, be ≥18 years of age (or at least the legal age of majority in the jurisdiction in which the study is taking place).
Disease Characteristics
Criterion modified per Amendment
2.1. Documented diagnosis of MM as defined by the criteria below:
a. MM diagnosis according to the IMWG diagnostic criteria (Rajkumar 2014).
b. Measurable disease at screening as assessed by central laboratory, defined by any of the following:
i. Serum M-protein level ≥0.5 g/dL; or
ii. Serum Ig FLC ≥10 mg/dL and abnormal serum IgκλFLC ratio; or
iii. Urine M-protein level ≥200 mg/24h
NOTE: In exceptional circumstances and after discussion with and written approval by the sponsor, local laboratory results may be used to determine initial eligibility, but only if the local results are clearly (≥25%) above the thresholds for measurability. In such cases, central laboratory results should still be obtained from samples collected prior to the start of study treatment to establish baseline values and confirm the results from the local laboratory.
Prior Therapy Restrictions or Requirements
Received at least 3 prior lines of antimyeloma therapy including a PI, an IMiD, and an anti-CD38 mAb.
Refer to Section 10.8 for the definition of a line of therapy.
Criterion modified per Amendment 1.
4.1. Documented evidence of PD or failure to achieve a response (ie, PR or better) to the last line of therapy based on investigator’s determination of response by the IMWG criteria.
NOTE: RR disease as defined below:
a. Relapsed disease is defined as an initial response to prior treatment, followed by confirmed PD by the IMWG response criteria >60 days after cessation of treatment.
b. Refractory disease is defined as failure to achieve a response (ie, PR or better) or confirmed PD by the IMWG response criteria during previous treatment or ≤60 days after cessation of treatment.
Have discontinued concurrent use of any other anticancer treatment (including nonpalliative radiotherapy) or investigational agent.
Toxicity related to prior anticancer treatment must have resolved to Grade 1 or better (except alopecia, skin fibrosis or discoloration, dry mouth, endocrinopathy managed with replacement therapy, peripheral neuropathy, and dysgeusia, which must be Grade 2 or better)
Performance Status
Have an ECOG PS of 0 to 2 at screening and immediately before the start of study treatment administration (Oken 1982).
Renal Function
Criterion modified per Amendment 1.
7.1. Have an eGFR, calculated with the CKD-epi creatinine formula (Section 10.12), of >30 mL/min during the Screening Period. See Note below the exclusion criteria table for details.
Hepatic Function
Participants are eligible if they have the following laboratory values during the Screening Period and within 1 day of the start of administration of study treatment
• AST and ALT <2.5×ULN
• Total bilirubin <1.5×ULN
• Bilirubin in case of known congenital nonhemolytic indirect hyperbilirubinemias such as Gilbert’s Syndrome Isolated total bilirubin ≥1.5×ULN with direct bilirubin <1.5×ULN
Hematologic Values
Participants are eligible if they have the following laboratory values during the Screening Period and within 1 day of the start of administration of study treatment
• Hemoglobin: ≥7.5 g/dL, without use of transfusion or growth factors within 1 week
• Neutrophils: ≥0.75×10 3 /µL (without use of G-CSF or GM-CSF within 1 week prior to the date of the laboratory test or 2 weeks for pegylated G-CSF)
• Platelets : ≥50×10 3/µL (without transfusion within 1 week, during the Screening Period and within 1 day of the start of administration of study treatment)
Participants must agree, while on study treatment and for 6 months after the last dose of study treatment, to:
• Not breastfeed or be pregnant.
• Not donate gametes (ie, eggs or sperm) or freeze for future use for the purposes of assisted reproduction.
• Wear an external condom, when transmission of sperm/ejaculate can occur.
• If of childbearing potential,
o Have a negative highly sensitive (eg, β-hCG) pregnancy test at screening and within 24 hours before the first dose of study treatment, and agree to further pregnancy tests
o Practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used.
• If able to produce sperm and their partner is of childbearing potential, the partner must practice a highly effective method of contraception.
See Section 10.3: Contraceptive and Barrier Guidance for details.
Exclusion Criteria
Medical Conditions
Criterion modified per Amendment
1.1. History of uncontrolled illness, including but not limited to:
a. Evidence of active systemic viral, fungal, or bacterial infection requiring systemic antiviral, antifungal, or antimicrobial therapy
b. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment. EXCEPTION: Participants with vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed or treated
c. Overt clinical evidence of dementia or altered mental statusSuspected or known allergies, hypersensitivity, or intolerance to excipients of JNJ-79635322 (refer to the IB)
Criterion modified per Amendment
3.1. Had major surgery within 2 weeks before first dose or has planned major surgery during study Treatment Phase. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.Active plasma cell leukemia at the time of screening (≥5% circulating PCs in peripheral blood smear), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis.
Cardiovascular Dysfunction
Any of the following within 6 months prior to first dose of study treatment: severe or unstable angina, myocardial infarction, seizure, major thromboembolic events (eg, pulmonary embolism, cerebrovascular accident [including TIA and stroke]), clinically significant ventricular arrhythmias or heart failure New York Heart Association functional classification Class III or IV. Uncomplicated deep vein thrombosis is not considered exclusionary.
Prior Malignancies
Participant has a prior or concurrent second malignancy (other than the disease under study) the natural history or treatment of which could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s) (see Section 10.5 on Allowed Recent Second or Prior Malignancies for details).
Brain and Central Nervous System Metastases
Known active or prior CNS involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain MRI and lumbar cytology are required.
Participant has leptomeningeal disease.
HIV Status
Participants who are HIV positive and meet any of the following:
a. Detectable viral load (ie, >50 copies/mL) at screening
b. CD4+ count <300 cells/mm3 at screening
c. AIDS-defining opportunistic infection within 6 months of screening
d. Receive treatment other than continued HAART. A change in HAART due to resistance/progression must occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.
Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment).
Viral Hepatitis Assessments
Active hepatitis of infectious origin.
a. Seropositive for hepatitis B: defined by a positive test for HBsAg. Participants with resolved infection (ie, participants who are HBsAg negative with positive antibodies to total hepatitis B core antigen must be screened using RT-PCR measurement of HBV-DNA levels). Those who are RT-PCR positive will be excluded. 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 RT-PCR. (see Section 10.7, Hepatitis B Virus Screening)
b. Known hepatitis C infection or positive serologic testing for hepatitis C virus (anti-HCV) antibody. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained at screening or within 3 months prior to first dose of study treatment.
c. Other clinically active liver disease of infectious origin.
Prior/Concomitant Therapy or Clinical Study Experience
Prior or concurrent exposure to any of the following, in the specified time frame prior to enrollment
a. T-cell redirection therapy (eg, CAR-T, bispecific antibody) within 6 months.
b. History of receiving both BCMA and GPRC5D-directed therapy.
c. An allogeneic stem cell transplant within 6 months before first dose of study treatment. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks before the start of study treatment administration without signs of graft-versus-host disease.
d. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14 days prior to first dose of study treatment.
Received or plans to receive any live, attenuated vaccine within 4 weeks before the first dose of study treatment, during, or 90 days after the last dose of JNJ-79635322. Nonlive and nonreplication-competent vaccines approved or authorized for emergency use by local health authorities are allowed.
Other Exclusions
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.
NOTE: Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study treatment is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study. The required source documentation to support meeting the enrollment criteria will be noted in Protocol Section 10.2.
5.3. Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions during the study to be eligible for participation:
- Carry a “wallet study card” with pertinent information for the duration of study participation.
The participant must be provided with a "wallet study card" which must contain (a) study number, site number, and participant’s study ID number, (b) statement, in the local language(s), that the participant is participating in this clinical study, (c) investigator's name and 24-hour contact telephone number, (d) local sponsor's name and 24-hour contact telephone number (for medical personnel only). - Agree to self-monitor for signs and symptoms of CRS (such as fever) and to seek immediate medical treatment.
- Any blood donation is not allowed until ≥90 days after the last dose of study treatment.
- Agree to follow all requirements that must be met during the study as noted in the Inclusion and Exclusion Criteria (eg, contraceptive requirements).
- Refer to Section 6.9.3 for details regarding prohibited and restricted therapy during the study.
