IRB Study Number 23-552
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
• To compare the efficacy of teclistamab with PVd/Kd
Secondary Objectives
• To further compare the efficacy of teclistamab with PVd/Kd
• To assess the safety profile of teclistamab
• To characterize the PK of teclistamab
• To assess the immunogenicity of teclistamab
• To assess participant’s symptoms, functioning, and HRQoL with teclistamab versus PVd/Kd
• To evaluate the efficacy of teclistamab in highrisk molecular subgroups
Inclusion Criteria
≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
Documented diagnosis of multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to IMWG diagnostic criteria (Appendix 4).
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) Serum immunoglobulin free light chain ≥10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio (see Appendix 4).NOTE: All attempts should be made to determine eligibility of the participant based on the central laboratory results of screening blood and urine M-protein measurements. In exceptional circumstances and after discussion with and written approval by the sponsor, the local laboratory results of blood and urine M-protein measurements may be used to determine initial eligibility, but only if the results are ≥25% above the thresholds for measurability. In such cases, central laboratory results should still be obtained prior to the start of administration of study treatment in order to establish baseline central laboratory values and confirm the results from the local laboratory.
- Relapsed or refractory disease as defined below:
a. Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease by IMWG criteria >60 days after cessation of treatment.
b. Refractory disease is defined as failure to achieve a response or confirmed progressive disease by IMWG criteria during previous treatment or ≤60 days after cessation of treatment.
Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti-CD38 monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line. NOTE: A single line of therapy may consist of 1 or more agents and may include induction, hematopoietic stem cell transplantation and maintenance therapy. Radiotherapy, bisphosphonates, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy (Appendix 19).
Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator’s determination of response by IMWG criteria.
Have an ECOG performance status score of 0 to 2 (Section 8.3.10, Appendix 5).
Have clinical laboratory values meeting the following criteria during the Screening Phase. In addition, these laboratory values must be re-evaluated within 3 calendar days prior to the first dose and the participant must also meet all criteria. If one or more criteria are not met within 3 calendar days prior to dosing, one repeat of laboratory testing is permitted. If >1 repeat laboratory test is necessary, the sponsor must be consulted prior to dosing.
A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test within 10 to 14 days prior to C1D1 and again either serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
A female participant must be either of the following (as defined in Appendix 8):
a. Not of childbearing potential, or
b. Of childbearing potential and practicing at least 2 effective methods of contraception simultaneously, including 1 highly effective method of contraception (details in Appendix 8). Contraception must begin 4 weeks prior to dosing, continue during study treatment, including during dose interruptions, and through 6 months after the last dose of study treatment. See Section 6.11.3 for details regarding concomitant use of hormonal products with pomalidomide and carfilzomib. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy (Appendix 8). NOTE: If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with (b) as described above.
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 a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anticancer treatments may impair fertility.
A male participant must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 3 months after receiving the last dose of study treatment If a male participant’s partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception (see Appendix 8). NOTE: If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception.
A male participant must agree not to donate sperm for the purpose of reproduction during the study and a period of 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility.
A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.
A male participant must agree not to plan to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
Must sign an ICF (or their legally acceptable representative must sign in accordance with local legislation) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 5.3).
Exclusion Criteria
Received any prior BCMA-directed therapy
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator’s Brochure and appropriate prescribing information). Additional exclusion criteria pertaining to specific study drugs include:
a. A participant is not eligible to receive PVd as control therapy if any of the following are present:
1) Received prior pomalidomide therapy.
2) Does not meet criteria for bortezomib retreatment (failure to achieve at least PR to prior bortezomib treatment, or progression by IMWG criteria on therapy or within 6 months after cessation of prior bortezomib treatment).
3) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib (intolerance defined as prior therapy discontinued due to any AE related to pomalidomide or bortezomib)
4) Grade 1 peripheral neuropathy with pain or Grade ≥2 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
5) Received a strong CYP3A4 inducer (see Section 6.11.3.3) within 5 half-lives prior to randomization
b. A participant is not eligible to receive Kd as control therapy if any of the following are present:
1) Received prior carfilzomib therapy.
2) Uncontrolled hypertension, defined as an average systolic blood pressure >159 mmHg or diastolic blood pressure >99 mmHg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology 2018 guidelines (Williams 2018).
3) Grade 2 peripheral neuropathy with pain or Grade ≥3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
4) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any AE related to carfilzomib)
c. Participants will be excluded for either of the following:
1) If they have previously received both carfilzomib AND pomalidomide
2) If they have previously received carfilzomib and do not meet criteria for bortezomib retreatment (as defined in Inclusion Criterion #2).
Participants will be excluded if intolerant to dexamethasone.
Received the following prior antimyeloma therapy, within the specified time frame prior to randomization:
a. 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
b. Investigational vaccine within 4 weeks
c. Monoclonal antibody therapy within 21 days
d. Cytotoxic therapy within 21 days
e. PI therapy within 14 days
f. IMiD agent therapy within 14 days
g. Radiotherapy within 14 days or focal radiation within 7 days
h. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NKcells) within 3 months
i. Plasmapheresis within 28 days
j. Received a maximum cumulative dose of corticosteroids of ≥140 mg of prednisone or equivalent within 14 days (see Appendix 10)
k. Stem cell transplant:
1) An allogeneic stem cell transplant within 6 months. Participants who received an allogeneic transplant must be off all immunosuppressive medications for ≥42 days without signs of graft‑versus‑host disease.
2) An autologous stem cell transplant within 12 weeks
Live, attenuated vaccine within 4 weeks of randomization or if participant plans to receive such vaccines during the study. Vaccines approved or authorized for emergency use (eg, COVID-19; see Appendix 22) and non-live vaccines (eg, influenza) are allowed.
CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
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.
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 malignancies treated within the last 24 months that are considered completely cured:
a. Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no CIS)
b. Skin cancer (non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone)
c. Noninvasive cervical cancer
d. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents
e. Localized prostate cancer (N0M0) with a Gleason Score <7a, treated locally only (RP/RT/focal treatment)
f. Other malignancy that is considered cured with minimal risk of recurrence. Note: In the event of any questions, consult with the sponsor’s medical monitor prior to enrolling a participant.
Stroke, transient ischemic attack, or seizure within 6 months prior to randomization.
Presence of the following cardiac conditions.
a. Unstable angina or New York Heart Association class III or IV congestive heart failure (Appendix 11)
b. Myocardial infarction or coronary artery bypass graft ≤6 months prior to randomization
c. History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
d. Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
e. TTE or MUGA scan showing left ventricular ejection fraction <40%
Participant had major surgery or had significant traumatic injury within 2 weeks prior to randomization, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study. NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is a question whether a procedure is considered a major surgery, the investigator must consult with the appropriate sponsor representative and resolve any issues before enrolling a participant in the study.
Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study, such as:
a. Acute diffuse infiltrative pulmonary disease or pulmonary hypertension
b. Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy
c. History of autoimmune disease with the exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing
d. Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status
e. History of non-compliance with recommended medical treatments
f. Intolerance to hydration due to preexisting pulmonary or cardiac impairment
g. Pleural effusions requiring thoracentesis within 14 days prior to randomization. Ascites requiring paracentesis within 14 days prior to randomization.
Seropositive for hepatitis B: defined by a positive test for HbsAg. Participants with resolved infection (ie, participants who are HbsAg negative with antibodies to total anti-HBc with or without the presence of anti-HBs) must be screened using RT-PCR measurement of HBV DNA levels. Participants with a known history of HBV infection must be screened using RT-PCR measurement of HBV DNA levels irrespective of serological results. 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 Appendix 9).
Active hepatitis C infection as measured by positive HCV-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study
Human immunodeficiency virus-positive with 1 or more of the following:
a. History of AIDS-defining conditions
b. CD4 count <350 cells/mm3
c. Detectable viral load during screening or within 6 months prior to screening
d. Not receiving highly active antiretroviral therapy
e. Had a change in antiretroviral therapy within 6 months of the start of screening
f. Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the sponsor.
- 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.
