A Phase 2, Open-label, Randomized Study to Evaluate Prophylactic Interventions on Talquetamab-related Oral Toxicity

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 May 2025 → ongoing

Decision date (initial)

2024-07-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Janssen Research & Development, LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Pharmacokinetic, Safety, Prophylaxis

To identify prophylaxis or prophylaxes that can minimize the incidence, severity, and duration of talquetamab-related dysgeusia, during the study Treatment Phase
To better characterize the clinical presentation of talquetamab-related dysgeusia.

Conditions and MedDRA coding

multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Both criteria below: a. MM according to IMWG diagnostic criteria (Appendix 5). b. Measurable disease at screening, as assessed by local laboratory, defined by any of the following: 1) Serum M-protein level ≥0.5 g/dL; or 2) Urine M-protein level ≥200 mg/24 hours; or 3) Light chain multiple myeloma without measurable M-protein in the serum or the urine: sFLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. 4) For participants without measurable disease in the serum, urine, or involved FLC, presence of plasmacytomas (≥2 cm).
2. Were triple-class exposed (received prior treatment with a PI, an IMiD, and anti-CD38 mAb).
3. Have clinical laboratory values meeting the following criteria in Table 4 during the Screening Phase and within 72 hours of the first dose of talquetamab. If 1 or more criteria are not met 72 hours prior to talquetamab dosing, one repeat of laboratory testing is permitted. Hematology: hemoglobin ≥8 g/dL; 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; absolute neutrophil count ≥1.0×109/L Chemistry: AST and ALT ≤3×ULN; eGRF ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation; total bilirubin <1.5×ULN; serum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L)
4. Human immunodeficiency virus-positive participants are eligible if they meet all of the following: a. No detectable viral load (ie, <50 copies/mL) at screening b. CD4+ count >300 cells/mm3 at screening c. No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening d. Receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to enrollment. A change in HAART due to toxicity is allowed up to 4 weeks prior to enrollment. Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment, if needed).
5. While on study treatment and for 3 months after the last dose of study treatment, a participant must: a. Not breastfeed or be pregnant b. Not donate gametes (ie, eggs or sperm) or freeze for future use for the purposes of assisted reproduction c. Use contraceptive(s) d. If of childbearing potential, 1) have a negative highly sensitive (eg, beta-human chorionic gonadotropin [β-hCG]) pregnancy test at screening and within 24 hours before the first dose of talquetamab treatment, and agree to further pregnancy tests, 2) practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used. e. If a participant’s partner is of childbearing potential, the partner must practice a highly effective method of contraception unless the participant is vasectomized. See Appendix 4 for details.

Exclusion criteria 6

1. Any of the following: a. Hepatitis B infection (hepatitis B surface antigen or HBV-DNA positive): In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status. See Section 8.4.7 for further required assessments. b. 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 for at least 12 weeks following the completion of therapy, the participant is eligible for the study.
2. A WETT score suggesting severe dysgeusia at screening. Also unresolved/severe dysgeusia referred by the participant or a finding in the physical examination/oral cavity inspection. Some examples include leukoplakia, prior mouth cancers, extensive dental caries, severe periodontitis, active oral infections, candidiasis, parotic gland removal, or radiotherapy with resultant xerostomia.
3. 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. Uncontrolled diabetes b. Acute diffuse infiltrative pulmonary disease. c. Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy. d. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of talquetamab. EXCEPTION: Participants with vitiligo, controlled 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. e. Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or severe impaired mental status that in the investigator’s opinion would compromise compliance with the study procedures. f. Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent or 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. g. History of noncompliance with recommended medical treatments.
4. Any of the following: a. Any history of malignancy other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy. b. Any ongoing B-cell malignancy (other than multiple myeloma) or myelodysplastic syndrome. c. Any 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 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) Noninvasive cervical cancer. 4) Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer (anti-antihormonal 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’s medical monitor.
5. Prior or concurrent exposure to any of the following, in the specified time frame prior to the start of talquetamab: a. Received any prior GPRC5D-directed therapy. b. T cell redirection therapy (eg, bispecific antibody therapy or bispecific T cell engager(s)) within 3 weeks. c. Gene-modified adoptive cell therapy (eg, CAR-T cells, natural killer cells) within 3 months. d. 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. e. Received or plans to receive any live, attenuated vaccine within 4 weeks before the first dose of study drug. Non-live vaccines approved or authorized for emergency use (eg, COVID 19) by local health authorities are allowed. f. Monoclonal antibody therapy within 21 days. g. Cytotoxic therapy within 21 days. h. PI therapy within 14 days. i. IMiD agent therapy within 14 days. j. Radiotherapy within 14 days or focal radiation within 7 days. Any radiotherapy to the oral cavity or anterior neck in the last 3 months.
6. Received either of the following: a. An allogeneic SCT within 6 months before the first dose of study treatment. Participants who received an allogeneic transplant must be off all immunosuppressive medications during the 6 weeks before the start of talquetamab without signs of graft versus host disease. b. An autologous SCT within 12 weeks before the start of talquetamab. c. A stem cell boost within 90 days before the first dose of talquetamab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. As determined by the total WETT testing score: - Rate of occurrence of taste dysfunction dysgeusia - Rate of occurrence of severe dysgeusia - Time to the first onset of severe dysgeusia - Rate of resolution/improvement of dysgeusia at the end of months 3 and 6

Investigational products

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

Test 11

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

Vit Novak

Public contact point

Organisation

Janssen - Cilag International

Contact name

Vit Novak

Third parties 7

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 33 files

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

Application history

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