Inclusion Criteria:
1. ≥18 years of age (or the legal age of majority, if greater than 18, in the jurisdiction in which the study is taking place) at the time of informed consent.
2. Documented diagnosis of multiple myeloma as defined by the criteria below:
1. Multiple myeloma diagnosis according to IMWG diagnostic criteria.
2. Measurable disease at screening as defined by any of the following:
1. Serum M-protein level ≥0.5 g/dL; or Serum Ig FLC ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
3. 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.
4. Received 1-3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti-CD38 monoclonal antibody at the approved dosing schedule (or minimum of 6 doses if anti-CD38 monoclonal antibody was only part of a maintenance 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.
5. 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.
6. Have an ECOG performance status score of 0 to 2
7. Have clinical laboratory values meeting the protocol criteria during the Screening Phase.
8. A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test within 14 days prior to first dose and again a negative serum pregnancy test within 24 hours of the start of study treatment and must agree to further serum pregnancy tests during the study.
9. A female participant must be either of the following a. Not of childbearing potential, or b. Of childbearing potential and practicing at least 1 highly effective method of contraception.
10. 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
11. 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.
12. 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 anti-cancer treatments may impair fertility.
13. Must sign an ICF (or their legally designated 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.
14. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Exclusion Criteria:
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Received any prior BCMA-directed therapy.
2. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab IB and appropriate prescribing information).
3. Participants will be excluded if intolerant to dexamethasone.
4. Received the following prior antimyeloma therapy, within the specified time frame prior to enrollment:
1. 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
2. Investigational vaccine within 4 weeks
3. Monoclonal antibody therapy within 21 days
4. Cytotoxic therapy within 21 days
5. PI therapy within 14 days
6. IMiD agent therapy within 14 days
7. Radiotherapy within 14 days or focal radiation within 7 days
8. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
9. Plasmapheresis within 28 days
10. Received a maximum cumulative dose of corticosteroids of ≥140 mg of prednisone or equivalent within 14 days
11. Stem cell transplant within 6 months. Participants who received an
5. Received a live, attenuated vaccine within 4 weeks of enrollment or if participant plans to receive such vaccines during the study. Non-live or non replicating vaccines authorized for emergency use are allowed.
6. CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology may be required.
7. Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis.
8. Excluded for any of the following:
1. Any ongoing myelodysplastic syndrome.
2. Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy.
3. Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured: Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, \<3 cm, no CIS), Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone.,Non-invasive cervical cancer, Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer (anti-hormonal therapy is permitted), Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment), Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor.
9. Stroke, transient ischemic attack, or seizure within 6 months prior to enrollment.
10. Presence of the following cardiac conditions.
a. Unstable angina or New York Heart Association class III or IV congestive heart failure, b. Myocardial infarction or coronary artery bypass graft ≤6 months prior to enrollment,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%
11. Participant had major surgery or had significant traumatic injury within 2 weeks prior to enrollment, 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.
12. Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or constitute a hazard for participating in the study (ie, those listed below) or any others 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 diagnosis of pulmonary hypertension. b. Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy.
c. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment. Exception: Participants with vitiligo. controlled type I diabetes, and prior autoimmune thyroid disease that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed. Eligibility for participants with any other autoimmune disease(s) should be discussed with the medical monitor/sponsor. 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 pre-existing pulmonary or cardiac impairment. g. Pleural effusions requiring thoracentesis within 14 days prior to enrollment. Ascites requiring paracentesis within 14 days prior to enrollment.
13. 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 have detectable HBV-DNA levels by RT-PCR 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.
14. Active hepatitis C infection as measured by detectable 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.
15. Human immunodeficiency virus-positive with 1 or more of the following:
1. History of AIDS-defining conditions
2. CD4+ count \<350 cells/mm3 during screening
3. Detectable viral load during screening or within 6 months prior to screening
4. Not receiving highly active antiretroviral therapy
5. Had a change in antiretroviral therapy within 6 months of the start of screening
6. Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the sponsor.
16. 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.
