Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Surovatamig · 7 trials · 13 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.
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.
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Surovatamig | DRUG | Surovatamig will be administered as a subcutaneous injection. |
| 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 |
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...
Surovatamig is an investigational small molecule being studied for B-cell Acute Lymphoblastic Leukemia (B-ALL), B-cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukaemia, Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated IGHV, Primary Membranous Nephropathy, and Rheumatoid Arthritis. It is being developed by AstraZeneca PLC (AZN) and is currently in Phase 1 clinical development.
Surovatamig is being developed by AstraZeneca PLC, a biopharmaceutical company traded on the stock exchange under the ticker symbol AZN. The drug is currently in Phase 1 clinical trials and is not yet approved by regulatory authorities.
Surovatamig is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by the FDA or other regulatory agencies. Clinical trials are ongoing to evaluate its safety and efficacy in various conditions, including B-cell malignancies and autoimmune diseases.
Surovatamig is being studied in several clinical trials. NCT07571746 is a Phase 2 study in Primary Membranous Nephropathy. NCT07509151 is a Phase 3 study in Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma with unmutated IGHV. NCT07201558 is a Phase 1 study in Rheumatoid Arthritis and Systemic Lupus Erythematosus. NCT06564038 is a Phase 1 study in B-cell malignancies.
Surovatamig is being studied in combination with AZD0486 in a clinical trial for mature B-cell malignancies. However, Surovatamig and AZD0486 are distinct investigational drugs. The trial NCT06564038 evaluates AZD0486 alone or with other anti-cancer agents, including Surovatamig.