Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AZD0486 IV, TNB-486, Surovatamig
AZD0486 · 9 trials · 17 indications
To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV.
PFS is defined as the time from date of randomisation until disease progression or death due to any cause, whichever occur first based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria, as assessed by independent review committee (IRC).
To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV.
Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
The RP3D will be the dose of AZD0486 selected for the Phase 3 part based on safety data compiled during the Safety Run-In part
Progression-free Surival (PFS), based on Lugano 2014 Response Criteria.
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures.
The RP3D will be the dose of Surovatamig selected for the Phase 3 part based on safety data compiled during the safety run-in part
PFS, based on Lugano 2014 Response Criteria, as assessed by BICR.
To assess the safety and tolerability of surovatamig on adverse events, including Adverse events, Serious adverse events, Adverse event of special interests, and Adverse events leading to discontinuation of surovatamig.
To assess the effect of surovatamig on proteinuria
Overall response summarized via overall response rate (ORR), defined as the proportion of participants achieving either a Partial Response (PR) or Complete Response (CR) based on Lugano 2014 response criteria for non-Hodgkin Lymphoma, as determined by central review
Number and percentage of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
Number and percentage of participants with DLTs (dose-limiting toxicities) as defined in the study protocol
Number of participants with AEs/SAEs leading to discontinuation of surovatamig
Number and percentage of participants with treatment-related vital signs abnormalities
Number of participants with treatment-related clinical laboratory abnormalities
Number and percentage of participants with abnormal ECG.
Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
DLTs are dose-limiting toxicities as defined in the study protocol
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
To evaluate the efficacy of surovatamig based on NCCN response criteria (in Part B and C).
To evaluate the efficacy of surovatamig in Part D based on NCCN response criteria. CR/CRh is defined as a best response of CR/CRh within 3 cycles.
A DLT is defined as a TEAE that is not unequivocally due to the subject's underlying malignancy or other extraneous cause. DLT evaluable subjects are defined as those subjects who receive either the target dose of AZD0486 or priming dose(s) in any step-up dose schedule and are assessed for toxicities for the 28-day evaluation period. The NCI-CTCAE version 5.0 will be used (except for CRS and NT). A DLT will be evaluated as Non-hematologic, Hematologic, Cytokine Release Syndrome (CRS), or neurotoxicity.
The incidence, timing, seriousness, and relationship to study treatment of adverse events will be evaluated.
The maximum observed serum concentration on a concentration time curve.
Area under the serum concentration-time curve from time zero to time of last measurable concentration.
Terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods.
| Arm | Type | Description |
|---|---|---|
| Dose Optimisation and Safety run-in (DOSRI)- Surovatamig Dose 1 | EXPERIMENTAL | Participants will receive Surovatamig Dose 1 subcutaneously (SC) for 6 cycles (each cycle is 28 days in length). |
| DOSRI-Surovatamig Dose 2 | EXPERIMENTAL | Participants will receive Surovatamig Dose 2 SC for 6 cycles (each cycle is 28 days in length). |
| Phase III-Arm A: Surovatamig SC | EXPERIMENTAL | Participants will receive Surovatamig at RP3D subcutaneously for 6 cycles (each cycle is 28 days in length). |
| Phase III-Arm B: Observation | NO_INTERVENTION | Participants will undergo observation for 24 weeks. |
| Phase III Arm A: R-mini-CHOP and AZD0486 | EXPERIMENTAL | 2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D. |
| Phase III Arm B: R-mini-CHOP | ACTIVE_COMPARATOR | 6 cycles of R-mini-CHOP per SoC regimen. |
| Safety Run in: R-mini-CHOP and AZD0486 | EXPERIMENTAL | 2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP2D. |
| Rituximab, Surovatamig - A | EXPERIMENTAL | Surovatamig regimen A plus rituximab |
| Rituximab, Surovatamig - B | EXPERIMENTAL | Surovatamig regimen B plus rituximab |
| Chemoimmunotherapy | ACTIVE_COMPARATOR | Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP, R-CVP, or B-R followed by rituximab maintenance) |
| Surovatamig Arm | EXPERIMENTAL | Participants will receive Surovatamig |
| Module 1: Surovatamig Monotherapy in Participants with Relapsed or Refractory Follicular Lymphoma | EXPERIMENTAL | In Module 1, the efficacy and safety of surovatamig at the RP2D will be evaluated in R/R FL. Surovatamig will be administered as intravenous infusion. |
| Module 2: Surovatamig Monotherapy in Participants with Relapsed or Refractory LBCL | EXPERIMENTAL | In Module 2, the efficacy and safety of surovatamig at the RP2D will be evaluated in R/R LBCL. Surovatamig will be administered as intravenous infusion. |
| Surovatamig | EXPERIMENTAL | Participants will receive Surovatamig subcutaneously in one of three dosing regimens: once (Part 1), twice (Part 2), or three times (Part 3), depending on the study part. |
| Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy) | EXPERIMENTAL | Participants will receive surovatamig monotherapy as subcutaneous (SC) injection. |
| Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib) | EXPERIMENTAL | Participants will receive surovatamig as SC injection. Participants will receive acalabrutinib tablet orally twice daily. |
| Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy) | EXPERIMENTAL | Participants will receive surovatamig monotherapy as intravenous (IV) infusion. |
| Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy) | EXPERIMENTAL | Participants will receive surovatamig monotherapy as SC injection. |
| Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy) | EXPERIMENTAL | Participants will receive surovatamig monotherapy as IV infusion. |
| Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP) | EXPERIMENTAL | Participants will receive surovatamig as IV infusion with a 2SUD (double step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. |
| Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP) | EXPERIMENTAL | Participants will receive surovatamig as IV infusion with a 3SUD (triple step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. |
| Part A: AZD0486 Dose Escalation | EXPERIMENTAL | Ascending dose level cohorts of surovatamig (AZD0486) in B-ALL participants aged 12 years and above. |
| Part B: Dose Optimization | EXPERIMENTAL | Up to 2 cohorts will be evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants, aged 12 years and above, will receive surovatamig (AZD0486) IV infusions and will be randomized in a 1:1 ratio. |
| Part C: Dose Expansion | EXPERIMENTAL | Part C will consist of 1 cohort of participants aged 12 years and above, treated with the optimal dose selected in Part B and receive IV surovatamig (AZD0486) monotherapy. |
| Part D: Dose Optimization and Efficacy Expansion in 2L+ | EXPERIMENTAL | Part D will enroll participants aged 12 years and above with Ph(+) and Ph(-) B-ALL relapsed/refractory to ≥1 prior line of therapy. Participants will be randomized 1:1 to 2 dose levels of surovatamig IV. |
| AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL | EXPERIMENTAL | AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. Depending on cohort, subjects may receive priming or step-up dosing administered weekly during cycle 1 before reaching the target dose. Additional cohorts may be opened where subjects receive weekly dosing during Cycles 1-2. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing |
| Name | Type | Description |
|---|---|---|
| Surovatamig | DRUG | Surovatamig will be administered as a subcutaneous injection. |
| AZD0486 | DRUG | Bispecific monoclonal IgG4 antibody |
| R-mini-CHOP | DRUG | Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2 |
| R-CHOP | DRUG | Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone |
| R-CVP | DRUG | Rituximab, Cyclophosphamide, Vincristine and Prednisone |
| BR | DRUG | Bendamustine, Rituximab |
| Prednisone (or equivalent) | DRUG | Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care. |
| Rituximab | DRUG | Rituximab will be administered as IV infusion as per standard of care. |
| Cyclophosphamide | DRUG | Cyclophosphamide will be administered as IV infusion as per standard of care. |
| Vincristine | DRUG | Vincristine will be administered as IV infusion as per standard of care. |
| Doxorubicin | DRUG | Doxorubicin will be administered as IV infusion as per standard of care. |
| Acalabrutinib | DRUG | Acalabrutinib will be administered orally |
| AZD0486 IV | DRUG | AZD0486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells leading to T cell-mediated cytotoxicity of malignant B cells |
Inclusion Criteria: * Documented diagnosis of CLL/SLL with genomic features defined by unmutated IGHV. * Treatment received and response at the end of 1L (first-line) finite therapy. * Participants with SLL (except those in CR in Phase III part) must have measurable disease (nodal or extranodal) wi...
AZD0486 is an investigational small molecule oncology drug being developed by AstraZeneca PLC for B-cell non-Hodgkin lymphoma and large B-cell lymphoma. It is in clinical development and is not described as approved. It is also known as AZD0486 IV.
AZD0486 is being studied for B-cell non-Hodgkin lymphoma and large B-cell lymphoma. One trial enrolls participants with diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and follicular lymphoma, while another studies it as first-line therapy in elderly or unfit participants with large B-cell lymphoma.
AZD0486 is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is the sponsor of the clinical trials evaluating AZD0486 in B-cell non-Hodgkin lymphoma and large B-cell lymphoma.
AZD0486 is in clinical development. It is listed as Phase 1, and a Phase 3 trial is also recruiting. AZD0486 is investigational and is not described as FDA approved.
AZD0486 is being studied in NCT04594642, a Phase 1 trial in B-cell non-Hodgkin lymphoma that is active but not recruiting, and NCT07215585, a recruiting Phase 3 trial of first-line therapy for elderly or unfit participants with large B-cell lymphoma.
Yes, AZD0486 IV is another name for AZD0486. Both refer to the same investigational AstraZeneca small molecule being studied in B-cell non-Hodgkin lymphoma and large B-cell lymphoma.