A Phase II, Open-label, Multicenter Study Testing Teclistamab in Combination with Pomalidomide Administered in Alternative Fashion in Participants with RRMM, who Received 1 - 3 Prior Lines of Therapy, Including Lenalidomide and Anti-CD38 Therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen Pharmaceutica NV - monetary and material support · Odense University Hospital - Material support (equipment, facilities, human ressources)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of teclistamab in combination with pomalidomide in alternate mode of administration

Secondary objectives 4

1. To further compare the efficacy of teclistamab in combination with pomalidomide in alternate mode of administration
2. To assess the safety profile of teclistamab in combination with pomalidomide in alternate mode of administration
3. To assess participant’s symptoms, functioning, and HRQoL with teclistamab in combination with pomalidomide in alternate mode of administration
4. To perform quantitative and qualitative analysis of T cell compartment and spatial characteristics of tumor microenvironment by flow cytometry, NGS Methylation Detection System, Spatial transcriptomics and by measurement of antiviral T responses during the treatment (ELISPOT).

Conditions and MedDRA coding

Multiple myeloma (RRMM)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 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. 2. 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; or 3) Serum Ig FLC ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
3. 3. Relapsed or refractory disease as defined below (and in Appendix 4): 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. 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 (Appendix 18).
5. 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 (Appendix 4).
6. 6. Have an ECOG performance status score of 0 to 2 (Section 8.3.9, Appendix 5).
7. 7. Have clinical laboratory values meeting the following criteria during the Screening Phase. Hematology Hemoglobin g/dL (5 mmol/L; recombinant human erythropoietin use is permitted) Platelets 75×109/L in participants in whom <50% of bone marrow nucleated cells are plasma cells and 50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) ANC 1.0×109/L (prior growth factor support is permitted) Chemistry AST and ALT ≤2.5×ULN eGFR ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation (Appendix 6) or creatine clearance measured by a 24-hour urine collection Total bilirubin ≤1.5×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required) Serum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L; see Appendix 7)
8. 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. 9. 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 1 highly effective method of contraception (see Appendix 8). See Section 6.11.3.2 for details regarding concomitant use of hormonal products with pomalidomide. NOTE: Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy (Appendix 8). NOTE: Participant of childbearing potential must agree to continue contraception from time of signing the ICF until 6 months after the last dose of study treatment. NOTE: If a female participant becomes of childbearing potential after the start of the study, or the risk of pregnancy changes, the female participant must comply with (b) as described above. If a participant’s reproductive status is questionable, additional evaluation should be considered. NOTE: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
10. 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 afterreceiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
11. 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 (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.
12. 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. 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. 14. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 5.3).

Exclusion criteria 16

1. 1. Received any prior BCMA-directed therapy.
2. 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. 3. Participants will be excluded if intolerant to dexamethasone.
4. 4. Received the following prior antimyeloma therapy, within the specified time frame prior to enrollment: 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, NK cells) 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
5. 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 (eg, COVID-19; see Appendix 20) are allowed.
6. 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. 7. Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis.
8. 8. Excluded for any of the following: a. Any ongoing myelodysplastic syndrome. b. Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy. c. 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: 1) Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no CIS) 2) Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone 3) Non-invasive cervical cancer 4) Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer (anti-hormonal therapy is permitted) 5) Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (RP/RT/focal treatment) 6) Other malignancy that is considered cured with minimal risk of recurrence in consultation with the sponsor. NOTE: In the event of any questions, consult with the sponsor’s medical monitor prior to enrolling a participant.
9. 9. Stroke, transient ischemic attack, or seizure within 6 months prior to enrollment.
10. 10. 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 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. 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. 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. 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 (see Appendix 9).
14. 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. 15. Human immunodeficiency virus-positive with 1 or more of the following: a. History of AIDS-defining conditions b. CD4+ count <350 cells/mm3 during screening 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.
16. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS at 12 months (12 cycles)

Secondary endpoints 12

1. MRD negative with CR after 12 cycles
2. MRD negative with CR after 24 cycles
3. PFS overall
4. ORR (PR or better)
5. VGPR or better
6. CR or better
7. Duration of response
8. Time to response
9. OS
10. Incidence and severity of AEs, Grade 3 or 4 infections, infection rate, serious AEs, AE Grade5/deaths and reasons, AEs causing treatment withdrawal or hospitalization and laboratory results
11. Change from baseline in symptoms, functioning, and overall HRQoL where baseline is defined as the latest measurement before the first dose of study treatment.
12. Time to worsening in symptoms, functioning, and overall HRQoL.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J. B. Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Jakub Krejcik

Public contact point

Organisation

Odense University Hospital

Contact name

Jakub Krejcik

Third parties 2

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications