A Phase 2, open-label study to evaluate the efficacy and safety of anitocabtagene autoleucel in participants with newly diagnosed multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion PETHEMA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Jun 2025 → ongoing

Decision date (initial)

2025-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fundación PETHEMA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety

To characterize the safety of anitocabtagene autoleucel following induction therapy in participants with newly diagnosed multiple myeloma
To further characterize the efficacy profile of anitocabtagene autoleucel following induction therapy in participants with newly diagnosed multiple myeloma

Secondary objectives 1

1. To further characterize the efficacy profile of anitocabtagene autoleucel following induction therapy in participants with newly diagnosed multiple myeloma

Conditions and MedDRA coding

Newly diagnosed multiple myeloma according to IMWG criteria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Newly diagnosed Multiple Myeloma according to the IMWG criteria published in 2014. a) For cohort A, patients will ≤ 70 years of age. b) For the cohorts B and C, patients will be ≤ 80 years of age
2. Measurable disease at screening per IMWG, defined as any of the following: a) Serum M-protein level ≥ 1 g/dL or urine M-protein level ≥ 200 mg/24 hours; or b) Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio. • Note: Local laboratory results may be used to establish measurable disease at screening if the results are ≥ 125% of requirements.
3. Only participants who are candidates to receive either D-VRd or Isa-VRd induction regimens, as determined by the investigator, should be considered for this study.
4. Male or female aged 18 years or older and has capacity to give informed consent.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Adequate hematological function defined as the following: ⎯ Hemoglobin count ≥ 7.5 g/dL (without any red blood cell [RBC] transfusion within 7 days prior to the test result; use of recombinant human erythropoietin is permitted). ⎯ Absolute neutrophil count (ANC) ≥ 500/μL (without non-PEGylated myeloid growth factor support within 7 days or PEGylated myeloid growth factor support within 14 days prior to the test result). ⎯ Platelet count ≥ 75,000/μL (unless secondary to bone marrow or spleen involvement of MM, in which platelet count ≥ 50,000/μL is permitted) without any platelet cell transfusion within 7 days prior to the test result. Bone marrow involvement by MM is demonstrated by bone marrow aspiration or biopsy. Spleen involvement by MM is demonstrated by splenomegaly. ⎯ Absolute lymphocyte count (ALC) ≥ 100/μL. ⎯ PTT/PT/INR < 1.5x upper limit of normal (ULN), unless on a stable dose of anticoagulant for a thromboembolic even (subjects with a history of thromboembolic stroke or history of Grade 2 or greater hemorrhage within 1 year are excluded.
7. Adequate renal, hepatic, pulmonary, and cardiac function defined as the following: ⎯ Estimated glomerular filtration rate (eGFR) (as estimated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation [Section 12.14]) ≥ 45 mL/min. ⎯ Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3  ULN. ⎯ Total bilirubin ≤ 1.5 mg/dL, except in participants with Gilbert’s syndrome or documented MM liver or pancreatic involvement where ≤ 3  ULN is permitted. ⎯ Cardiac ejection fraction ≥ 45% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO). Multigated acquisition (MUGA) scan may be used if an ECHO is not available at the site. ⎯ No evidence of Grade 2 or higher (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) pleural effusion or ascites (participants with Grade 1 pleural effusion or ascites are eligible). ⎯ Baseline oxygen saturation >92% on room air.
8. Females of childbearing potential must have a medically supervised negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
9. Willing to comply with and able to tolerate study procedures, including consent to participate in separate Long-term Safety Follow-up lasting up to 15 years per authorities´ guidance.

Exclusion criteria 25

1. Active or prior history of central nervous system (CNS) or meningeal involvement of MM.
2. Cardiac atrial or cardiac ventricular MM involvement.
3. Diagnosis of primary amyloidosis (AL), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia (PCL), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or Waldenstrom’s macroglobulinemia at the time of screening.
4. Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted. Allowed malignancy exceptions are: a) Localized skin cancer (melanoma and nonmelanoma) that has been completely resected and considered curative within the last 24 months is eligible. b) Cervix carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible. c) Bladder carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible. d) Breast carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible. Hormonal therapy after curative-intent treatment is permitted. e) Prostate cancer that is low grade and localized (Grade Group 1, has not spread to nearby lymph nodes [N0] or metastasized [M0]) within the last 24 months is eligible, including cases under surveillance only as part of standard of care. Androgen deprivation therapy is permitted. f) Localized renal cell carcinoma (≤ Stage 2) that has been completely resected and considered curative within the last 24 months is eligible. g) Localized (Stage 1) colorectal cancer that has been completely resected and considered curative (without need for adjuvant chemotherapy) within the last 24 months is eligible.
5. Any prior systemic anti-myeloma treatment (including BCMA-directed treatment) and/or radiotherapy before enrollment. Palliative radiation and corticosteroids (up to cumulative dose of 160mg prednisone or equivalent, and not requiring ongoing therapy) prior to enrollment are permitted. Participants must have recovered from all radiation-related toxicities. Patients with radiation-induced lung injury (RILI, radiation pneumonitis) during screening are excluded.
6. Prior allogeneic stem cell transplant (allo-SCT) (even if for another malignancy)
7. Live vaccine ≤ 4 weeks before enrollment and/or anticipating needing the vaccine during study period.
8. Presence or suspicion of fungal, bacterial, viral, or other infection that is systemic uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if the participant is responding to active treatment and satisfies the criteria of being afebrile (i.e., temperature < 38°C) for at least 24 hours prior to the investigator confirming the participant’s eligibility.
9. Acute or chronic active hepatitis A, B, or C infection. Participants with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines.
10. Human immunodeficiency virus (HIV)-seropositive.
11. Participants with history or presence of chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal will not be permitted to receive anti-CD38 monoclonal antibody in combination with VRd therapy; Note: FEV1 testing is required for participants who are planned
12. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months before enrollment. a. History or presence of intracranial or CNS disorder, such as hemorrhage, dementia, altered mental status, cerebellar disease, or any autoimmune disease with CNS involvement, PRES, or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication. Patient with history of neurodegenerative disease (e.g., Parkinson’s or Alzheimer’s disease) must be excluded.
13. Peripheral neuropathy of Grade 3 or higher (per CTCAE v5.0; participants with Grade 2 peripheral neuropathy are eligible).
14. History of solitary plasmacytoma
15. History of autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in or requiring systemic immunosuppression or systemic disease-modifying agents within 2 years.
16. History of concomitant genetic syndrome associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome.
17. History of DVT or PE within 6 months before enrollment. Anticoagulants (e.g., warfarin, low-molecular weight heparin, Factor Xa inhibitors) are allowed if DVT/PE occurred > 6 months before enrollment, and if the participant is on a stable maintenance dose.
18. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J-tube, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted.
19. Major surgery within 28 days before enrollment, or planned surgery required during study participation.
20. Any medical, neurologic or psychiatric condition that in the investigator’s opinion is likely to interfere with study procedures including assessment of safety or efficacy of the study treatment.
21. Females who are pregnant or breastfeeding (due to the potentially dangerous effects of the lymphodepleting chemotherapy or induction regimen on the fetus or infant).
22. Participants of both sexes who are not willing to practice highly effective birth control from the time of consent through 12 months following lymphodepleting chemotherapy administration, 12 months after the completion of anitocabtagene autoleucel, 5 months after the last dose of isatuximab, 3 months after the last dose of daratumumab, bortezomib, or 28 days after the last dose of lenalidomide, whichever is longer (refer to Section 12.2). Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential. Participants of both sexes must also comply with any relevant REMS or aRMMs as part of an RMP.
23. As per the investigator’s judgment, the participant is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with or tolerate the study requirements for participation (e.g., participants who are at a risk for a thromboembolic event and are not willing to take venous thromboembolism prophylaxis should be excluded).
24. Contraindication to fludarabine or cyclophosphamide.
25. History of allergy or hypersensitivity to any study agent or study drug components. Participants with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence, seriousness, and severity of all AEs
2. uMRD negative CR rate (minimum 10−5) at 12 months (+/- 3 months) after enrollment

Secondary endpoints 22

1. uMRD negative CR rate (minimum 10−5) at 2, 6, 12, 18 and 24 months after CAR T infusion and sustained uMRD annually
2. CR rate (CR (sCR), as assessed by investigators according to the International Myeloma Working Group (IMWG) criteria
3. Overall MRD negativity (minimum 10−5)
4. MRD-negative CR at any timepoint scheduled
5. Rate of conversion from undetectable to detectable MRD as well as biochemical progression rate
6. Time to biochemical progression (including the conversion from undetectable to detectable MRD).
7. undetectable MRD at 10-6
8. ORR per IMWG criteria
9. DoR
10. VGPR and PR rate per IMWG criteria
11. Time to initial response
12. PFS
13. Overall rate of “imaging plus MRD negative” (using PET/CT per IMWG)
14. Mass spectrometry MRD
15. Expansion and persistence of anitocabtagene autoleucel in peripheral blood
16. Characterize baseline tumor burden impact on efficacy, safety and cell expansion
17. Assess relationship of MRD-negativity to response, progression, and survival
18. Explore efficacy in high-risk populations (EMD, high-risk cytogenetics, ISS stage III, etc)
19. Characterize baseline soluble BCMA (sBCMA) and impact of Isa-VRd induction prior to anitocabtagene autoleucel and relationship to efficacy and safety
20. Characterize drug product attributes and relationship to efficacy and safety
21. Immunoprofiling by MFC in bone marrow and peripheral blood including identification and characterization of anitocabtagene autoleucel by MFC.
22. Overall survival

Investigational products

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

Test 1

Auxiliary 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion PETHEMA

Sponsor organisation

Fundacion PETHEMA

Address

Oficinas 3 4 5, Calle De Santa Balbina 2 Calle De Santa Balbina 2

City

Madrid

Postcode

28023

Country

Spain

Scientific contact point

Organisation

Fundacion PETHEMA

Contact name

Juan José Lahuerta Palacios

Public contact point

Organisation

Fundacion PETHEMA

Contact name

Juan José Lahuerta Palacios

Locations

1 EU/EEA country · 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 7 files

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

Application history

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