Teclistamab for people with previously treated AL amyloidosis

A Phase II Trial of Teclistamab in Participants With Previously Treated Immunoglobulin Light-chain (AL) Amyloidosis

This study tests whether teclistamab can help people with AL amyloidosis whose disease has returned or not responded to prior treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: European Myeloma Network B.V. (network)
• Drugs / interventions: teclistamab
• Locations: 10 sites (Adelaide and 9 other locations)
• Trial ID: NCT06649695 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label phase 2 trial gives teclistamab to participants who have previously received treatment for immunoglobulin light-chain (AL) amyloidosis. Teclistamab is a bispecific antibody that binds BCMA on the disease-causing plasma cells and CD3 on T cells to redirect immune attack against the plasma-cell clone. Participants receive protocolized dosing and are followed for hematologic response, organ responses, and safety outcomes. The single-arm study measures response rates and adverse events to determine whether the drug shows sufficient activity to support further development in this population.

Who should consider this trial

Good fit: Adults with biopsy-proven and properly typed AL amyloidosis who have received prior therapy and meet the trial's organ function and safety criteria are the intended participants.

Not a fit: Patients whose amyloid is due to transthyretin (ATTR), who have prohibitive organ failure, or who cannot tolerate immune-engaging therapies are unlikely to benefit.

Why it matters

Potential benefit: If successful, teclistamab could reduce the abnormal light-chain–producing plasma cells and potentially improve blood markers and organ function in people with relapsed AL amyloidosis.

How similar studies have performed: BCMA-targeting agents such as teclistamab have produced notable responses in multiple myeloma, but applying bispecific T-cell therapy to AL amyloidosis is a newer approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

* Histologic diagnosis of AL amyloidosis and typed with immunohistochemistry/ immunofluorescence, immunoelectron microscopy, or mass spectrometry. In patients with biopsy-confirmed amyloidosis, ambiguous amyloid typing results, and cardiac involvement alone, a negative pyrophosphate (PYP) or technetium-99m (99mTc) and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD-Tc99m) bone scan is required to distinguish cardiac involvement due to AL amyloidosis from amyloid transthyretin (ATTR) amyloidosis. Data from the initial diagnosis are accepted.
* Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis, or immunohistochemistry/ immunofluorescence/ immunoelectron microscopy/ mass spectrometry of amyloid deposits must provide clear evidence of κ or λ light chains in patients who present with peripheral neuropathy or heart as the dominant organ involvement. Data from the initial diagnosis are accepted.
* Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2
* Mayo stage I-IIIA cardiac disease at Screening
* Relapsed patients must have received at least 1 line of treatment, including Dara and bortezomib. Patients must have received at least two cycles of therapy. However, patients who have received high-dose therapy with melphalan as their only therapy are also eligible.
* Measurable hematologic disease: a dFLC \>20 mg/L with an abnormal κ/λ ratio (with Freelite® test kits, The Binding Site) or presence of a monoclonal spike ≥0.5 g/dL.
* Adequate bone marrow function, without transfusion or growth factors within 5 days prior to the first drug intake (C1D1), defined as:
* Absolute neutrophils ≥1,000/mm3,
* Platelets ≥75,000/mm3,
* Hemoglobin ≥8.5 g/dL.
* Adequate organ function, defined as:
* Serum creatinine clearance (CKD-EPI formula) ≥20 mL/min,
* Serum SGPT/ALT \<5.0 x Upper Limit of Normal (ULN),
* Serum total bilirubin \<2.0 mg/dL or direct bilirubin ≤30% of the total, unless the patient has Gilbert's syndrome, where direct bilirubin should then be \<2.0 mg/dL,
* Serum albumin ≥\<2.5 gr/dl (medication to correct serum albumin levels is permitted).

Exclusion Criteria:

* Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis.
* Isolated soft-tissue involvement.
* Presence of non-AL amyloidosis.
* Previous anti-BCMA targeted therapy (including, but not limited to, bispecifics).
* Intolerance to dexamethasone that would prohibit treatment with trial therapy.
* MM diagnosed as per the International Myeloma Working Group (IMWG) criteria, with the exception of monoclonal gammopathy of unknown significance (MGUS) or smoldering Myeloma, not requiring treatment.

Note: A MM diagnosis with a serum FLC ratio \>100, as the only myeloma-defining event, does NOT constitute an exclusion.

* All hematologic malignancies, with the exception of low-risk Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms (MPNs) and low-risk myelodysplastic syndromes (MDS), not requiring treatment.
* Mayo stage IIIB cardiac disease at Screening

Where this trial is running

Adelaide and 9 other locations

• South Australia Health — Adelaide, Australia (RECRUITING)
• Westmead Hospital — Sydney, Australia (RECRUITING)
• CHU Limoges — Limoges, France (RECRUITING)
• Paris St Louis — Paris, France (NOT_YET_RECRUITING)
• University Hospital Essen — Essen, Germany (RECRUITING)
• University Hospital Heidelberg — Heidelberg, Germany (RECRUITING)
• University Hospital Würzburg — Würzburg, Germany (RECRUITING)
• General Hospital of Athens "Alexandra" — Athens, Greece (RECRUITING)
• Fondazione I.R.C.C.S Policlinico "San Matteo" — Pavia, Italy (RECRUITING)
• UMC Utrecht — Utrecht, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Murielle Roussel, MD — CHU Limoges
• Study coordinator: Chiara Del Pietro

Conditions: AL Amyloidosis, teclistamab