Talquetamab (GPRC5D and CD3 antibody) in Relapsed or Refractory Multiple Myeloma

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

26 Apr 2018 → ongoing

Decision date (initial)

2024-03-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504581-29-00

EudraCT number

2017-002400-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Pharmacodynamic, Safety

To characterize the safety of talquetamab and recommend the Phase 2 dose(s) and schedule
To further characterize the safety of talquetamab at the recommended Phase 2 dose(s)
To evaluate the efficacy of talquetamab at the recommended Phase 2 dose(s)
The objectives of Cohort D are to evaluate the safety, PK, ADAs, and efficacy of talquetamab in subjects who receive tocilizumab prophylaxis for CRS
The objectives of Cohort E are to evaluate the safety, PK, ADAs, and efficacy of talquetamab using tocilizumab prophylaxis for CRS with consolidated priming dose schedules as well as potential outpatient priming.

Conditions and MedDRA coding

Multiple myeloma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. ≥18 years of age
2. Documented initial diagnosis of multiple myeloma according to IMWG diagnostic a criteria
3. Part 1: - Subjects with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: - Subjects with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%. Part 3: Measurable disease Cohort A, B and Cohort C: Multiple myeloma must be measurable by central laboratory assessment: - Serum M-protein level ≥1.0 g/dL or urine Mprotein level ≥200 mg/24 hours; or - Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%. Cohort E: Multiple myeloma must be measurable by local laboratory assessment: - Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or - Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. Prior treatment - Cohort A and Cohort C: have previously received ≥3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have not been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies. - Cohort B: have previously received ≥3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies. Cohort D: have previously received ≥3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody regardless of exposure to prior T cell redirection therapies such as CAR- T or bispecific antibodies. Cohort E: have previously received at least one PI, one IMiD, and one anti-CD38 monoclonal antibody regardless of exposure to prior T-cell redirection therapies such as CAR-T or bispecific antibodies. All Cohorts: Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease was the best response to the line of therapy. Subject must have documented evidence of progressive disease based on investigator’s determination of response by the IMWG 2016 criteria on or within 12 months of their last line of therapy*. Also, subjects with documented evidence of progressive disease within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible. *Criteria for progressive disease on or within 12 months of therapy does not apply to patients with CAR-T as last line of therapy (ie, Cohort B, D, and E).
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 for Parts 1 and 2 and 0-2 for Part 3 of the study
5. Pretreatment clinical laboratory values meeting the predefined criteria during the Screening Phase

Exclusion criteria 13

1. Prior Grade 3 CRS or higher related to any T cell redirection (eg, CD-3 redirection technology or CAR-T cell therapy) or any prior GPRC5D targeting therapy
2. Prior antitumor therapy as follows, prior to the first dose of study drug: - Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells [CAR-T], natural killer [NK] cells) within 3 months. - Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. - Monoclonal antibody treatment for multiple myeloma within 21 days. - Cytotoxic therapy within 21 days. - Proteasome inhibitor therapy within 14 days. - Immunomodulatory agent therapy within 7 days. - Radiotherapy within 14 days. However, if palliative focal radiation is used, the subject is eligible irrespective of the end date of radiotherapy. Part 3 only: - Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. - Cohort B, D, and E: T cell redirection therapy within 3 months
3. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
4. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication).
5. Received either of the following: - An allogenic stem cell transplant within 6 months before first dose of study drug. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft versus host disease (GVHD). - An autologous stem cell transplant ≤12 weeks before first dose of study drug
6. Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.
7. Plasma cell leukemia (>2.0 x 10 to the 9th/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes), or primary amyloid light chain amyloidosis.
8. Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome.
9. Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status. Active Hepatitis C infection as measured by positive HCV-RNA testing. Subjects with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing.
10. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation.
11. Known allergies, hypersensitivity, or intolerance to talquetamab or its excipients.
12. Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration. (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate).
13. Any potential subject who meets any of the following criteria will be excluded from participating in Part 3: Stroke or seizure within 6 months prior to signing the ICF The following cardiac conditions: - New York Heart Association Stage III or IV congestive heart failure - Myocardial infarction or coronary artery bypass graft (CABG) ≤6 months prior to enrollment - History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration - History of severe non-ischemic cardiomyopathy. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1 and Part 2: Frequency and type of DLT; frequency and severity of adverse events, serious adverse events, and laboratory abnormalities
2. Part 3: ORR (PR or better) as defined by the IMWG criteria based on review by the IRC
3. Occurrence and severity of TEAEs, serious TEAEs, adverse events of clinical interest, and ORR [PR or better], DOR, VGPR or better/CR or better/sCR, TTR, PFS, and OS.

Investigational products

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

Test 8

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

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 7

Locations

6 EU/EEA countries · 30 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 85 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