Relapsed/refractory chronic lymphocytic leukemia (CLL), multiple myeloma (MM), or acute myeloid leukemia (AML)
Conditions
Interventions
Product Name: LAVA-051
Product Code: LAVA-051
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: LAVA-051
Other descripti
Sponsors
LAVA Therapeutics N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be 18 years of age inclusive or above, at the time of signing the informed consent 2. Patients with documented diagnosis of CLL, MM, or AML who have failed to respond to or who have relapsed after prior therapy and are not amenable to standard treatments or for whom no standard treatments are available. Patients may have undergone prior cell therapy 2.1. CLL/ Small Lymphocytic Lymphoma (SLL) patients: 2.1.1. Proven disease by the presence of CD5+CD19+CD23+ clonal B cells in blood, bone marrow and/or lymph nodes. 2.1.2. Patients should meet criteria for requiring therapy (the most recent iwCLL guidelines (39)) and must have measurable disease (measurable lesion > 1.5 cm diameter in at least one dimension) and/or lymphocytosis 2.1.3. Patients must have received at least 2 prior lines of therapy and must have failed at least one line of targeted therapy (ibrutinib or venetoclax or similar) and not be amenable to- or for whom no further standard treatment is available 2.2. MM patients: 2.2.1. Documented diagnosis of MM and measurable disease (see Appendix 6, Section 13.6.2; measurable disease is defined as serum monoclonal paraprotein (M-protein) = 5 g/L or urine M-protein = 200 mg/24 hours or abnormal free light chain (FLC) ratio with involved FLC > 100 mg/L or proven plasmacytoma by biopsy*) 2.2.2. Documented progression or refractory multiple myeloma as per the IMWG uniform response criteria (see Appendix 6, Section 13.6.3) following =3 prior regimens that include at least one immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody in any order. * If plasmacytoma is the only measurable parameter, the patient is not allowed to be included in the trial, because of difficult response evaluation. 2.3. AML patients: 2.3.1. Patients with relapsed/refractory AML (defined using World Health Organization [WHO] most recent classification) of any type with the exception of acute promyelocytic leukemia (APL; AML M3). [Patients with a myelomonocytic or monocytic lineage (M4, M5) are most likely to be positive for the CD1d expression]. 2.3.2. Patients with relapsed/refractory AML (defined as hematologic relapse, molecular relapse, or primary refractory disease as per most recent ELN guidelines). 3. Males or non-pregnant, non-breastfeeding females who are: a. Surgically sterile (hysterectomy, bilateral oophorectomy or bilateral salpingectomy, vasectomy). b. Female of childbearing potential with a negative pregnancy test prior to first dosing and compliant with a highly effective contraceptive regimen (i.e., pregnancy rate of 40 IU/L). d. Male, compliant with an effective contraceptive regimen (i.e., use of male condom with female partner and assuring use of an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant following from signing of the ICF through 90 days after the last
Exclusion criteria
Exclusion criteria: 1. Prior allogeneic bone marrow transplant if the patient still has active acute or chronic graft versus host disease requiring >10 mg prednisone or equivalent corticosteroids. 2. Concomitant malignancies except carcinoma in situ, basal or squamous cell skin carcinoma. Patients who had no evidence of disease from another primary cancer for 2 or more years are allowed to participate in the trial. Localized non-metastatic prostate cancer, not requiring systemic treatment, and for which no local treatment is planned, is allowed. 3. Uncontrolled or severe intercurrent medical condition. 4. Known uncontrolled central nervous system involvement. 5. Patient has any active-, uncontrolled-, or suspected infection. 6. A significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect the patients' participation in this trial. 7. Unstable cardiovascular function defined as: (a) symptomatic ischemia, or (b) uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block (will not be excluded), or (c) congestive heart failure New York Heart Association Class = 3, or (d) myocardial infarction within 3 months or (e) QTc > 480 msec using Fredericia’s QT correction formula. 8. Previous treatment with radiotherapy, targeted therapy, investigational product, or chemotherapy in the 2 weeks (or 4 weeks for previous T-cell directed immunotherapy if requested by specific regulatory authorities) prior to initial IMP administration. 9. Previous treatment with an aminobisphosphonate IV (e.g., ibandronate, pamidronate, zoledronate etc) within 4 weeks prior to initial IMP. 10. Previous treatment of any systemic immunosuppressant within 2 weeks prior to initial IMP administration, with the exception of systemic corticosteroid use up to oral dose of 10 mg prednisolone daily (or equivalent for other steroids). 11. Previous treatment with live or live attenuated vaccines within 2 weeks prior to initial IMP administration. 12. Previous autologous haematopoietic stem cell transplantation (HSCT) or treatment with Chimeric Antigen Receptor (CAR) T-cell therapy within 6 months prior to initial IMP administration. 13. Known non-CLL/MM/AML related pre-existing clinically relevant immunodeficiency disorders. 14. Patients with Richter’s transformation are excluded. 15. Positive serological testing for Human Immunodeficiency Virus (HIV) antibody, hepatitis B surface antigen [HBsAg] and hepatitis B core antibody (anti-HBc) negative, and hepatitis C virus antibody. Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks prior to initial IMP administration. Those who are PCR positive will be excluded. 16. Known allergies, hypersensitivity, or intolerance to the excipients of the IMP or IL-2. 17. Major surgery within 4 weeks of initial IMP administration or planned surgery during the time the patient is expected to participate in the trial. 18. Known ongoing drug and alcohol abuse in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 Dose Escalation • To investigate the safety and tolerability of LAVA-051 in patients with relapsed/refractory CLL, MM, or AML • To determine the recommended Phase 2a dose (RP2D) of LAVA-051 in patients with relapsed/refractory CLL, MM or AML Part 2 Dose Expansion • To confirm the safety and tolerability of LAVA-051 in diseases specific dose expansion cohorts.;Secondary Objective: Part 1 Dose Escalation and Part 2 Dose Expansion • To explore the preliminary antitumor activity of LAVA-051. • To evaluate the pharmacokinetics of LAVA-051. • To evaluate the immunogenicity of LAVA-051.;Primary end point(s): Part 1 Dose Escalation • Frequency and severity of Adverse Events using the Common Terminology Criteria and grading for Adverse Events (CTCAE version 5.0) and American Society for Transplantation and Cellular Therapy (ASTCT) grading for CRS. • Frequency and type of DLT. Part 2 Dose Expansion • Frequency and severity, applying CTCAE and ASTCT grading, of AEs at the respective P2D.;Timepoint(s) of evaluation of this end point: Part 1 AEs are monitored continuously from ICF signature until the FU visit. DLT is defined as an AE and is occurring during Cycle 1 (28 days). Part 2 Anti-tumor response will take place: 1) CLL: screening, Peripheral blood at predose of C1-6D1, CT-scan of neck/chest/abdomen in the C3-4th wk, Peripheral Blood MRD at predose of C4D1, BM biopsy in case of suspected remission based on CT analysis and blood evaluation and EoT. 2) MM: screening, Blood/24-h urine at predose of C1-6D1, BM biopsy in C3-4th wk and for confirmation of CR or at disease progression, CT-scan as clinically indicated to document progression and in the C3-4th wk, PE at predose of C1-6D1, and EoT. 3) AML: screening, Peripheral blood at predose of C1-6D1, BM biopsy in the C3-4th wk, MRD of C4D1 and EoT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 Dose Escalation and Part 2 Dose Expansion • Antitumor Response: o For CLL patients: Response according to the most recent International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guideline. o For MM patients: Response according to the most recent International Myeloma Working Group (IMWG) criteria. o For AML patients: Response according to the most recent most recent European LeukemiaNet (ELN) criteria criteria. • Pharmacokinetic parameters. • Presence or development of anti-LAVA-051 antibodies ;Timepoint(s) of evaluation of this end point: PK collection: SCR, C1D1 at predose, C1D1 1h after SoI, EoI, 15min after EoI, 30min after EoI, 1h, 1,5h, 2h, 3h, 4h, 6h, 8h and 12h after EoI, 24h, 36h, 48h, 72h and 96h after SoI; C1D2-D4-D6 at predose and EoI; C1D3 predose, EoI, 24h and 48h after SOI; C2D1 predose, EoI, 1h, 2h and 4h after EoI, 24h and 48h after SoI; C3-6D1 predose and EoI; EoT | — |
Countries
France, Italy, Netherlands, Spain, United States
Contacts
Public ContactClinical Operations
LAVA Therapeutics N.V.
Outcome results
None listed