Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as JNJ-74494550, ARGX-110, OV-1001
Cusatuzumab · 6 trials · 4 indications
Complete remission based on European Leukemia Network (ELN) 2017 response criteria. Defined as bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absences of extramedullary disease; ANC \>= 1.0 x10\^9/L; platelet count \>=100 x 10\^9/L
Number of participants with AEs and SAEs will be reported.
Number of participants with DLTs will be reported.
Severity of DLT as assessed by NCI-CTCAE in participants will be reported.
DLT is defined as drug-related grade 3 or 4 clinical adverse event (AE) occurring during the 21 days (3 weeks) following the first dose of ARGX-110.
DLTs will be defined as any of the following drug-related events: Any grade 3 or higher drug related non-hematological toxicity or; Grade 3 or higher IRRs or; inability to administer the next dose due to a drug-related adverse event or a delay of the administration of the next dose due to toxicities for more than 14 days despite adequate medication or; drug-related grade 4 febrile neutropenia or; drug-related grade 4 anemia which cannot be adequately treated.
ORR is defined as the sum of Complete remission (CR), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) at the ARGX-110 RP2D level that was established in Phase 1 according to established response criteria for Acute myeloid leukemia (AML).
Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.
Change from baseline in incidence and grading of AEs according to the Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03
| Arm | Type | Description |
|---|---|---|
| Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg | EXPERIMENTAL | Participants will receive azacitidine 75 milligram per meter square (mg/m\^2) subcutaneously (SC) or intravenously (IV) on Day 1 through Day 7 and cusatuzumab 10 milligram per kilogram (mg/kg) IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee. |
| Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg | EXPERIMENTAL | Participants will receive azacitidine 75 mg/m\^2 SC or IV on Day 1 through Day 7 and cusatuzumab 20 mg/kg IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee. |
| Part 1 (Dose Finding): Cusatuzumab + Azacitidine | EXPERIMENTAL | Participants with acute myeloid leukemia (AML) will receive cusatuzumab intravenously (IV) in combination with azacitidine subcutaneously (SC) or IV. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. |
| Part 2 (Dose Expansion): Cusatuzumab + Azacitidine | EXPERIMENTAL | Participants with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) will receive cusatuzumab intravenously (IV) at the recommended Phase 2 dose (RP2D) determined in Part 1 in combination with azacitidine subcutaneously (SC) or IV. |
| Dose Escalation: Cohort 1 | EXPERIMENTAL | Participants will receive ARGX-110 as an intravenous infusion (IV) at dose level 1. |
| Dose Escalation: Cohort 2 | EXPERIMENTAL | Participants will receive ARGX-110 as an IV infusion at dose level 2. |
| Dose Escalation: Cohort 3 | EXPERIMENTAL | Participants will receive ARGX-110 as an IV infusion at dose level 3. |
| Dose Escalation: Cohort 4 | EXPERIMENTAL | Participants will receive ARGX-110 as an IV infusion at dose level 4. |
| Dose Escalation: Cohort 5 | EXPERIMENTAL | Participants will receive ARGX-110 as an IV infusion at intermediate dose level at the conclusion of Cohort 4 prior to opening the safety expansion cohorts to participants enrolment. |
| Safety Expansion: Cohort 1 | EXPERIMENTAL | Participants with solid tumors will receive ARGX-110 as an IV infusion at a dose based on the safety, PD, and PK profiles of ARGX-110 as per the dose escalation part of the trial. |
| Safety Expansion: Cohort 2 | EXPERIMENTAL | Participants with hematological malignancies (all etiologies) will receive ARGX-110 as an IV infusion at a dose based on the safety, PD, and PK profiles of ARGX-110 as per the dose escalation part of the trial. |
| Safety Expansion: Cohort 3 | EXPERIMENTAL | Participants with cutaneous T-cell lymphoma (CTCL) will receive ARGX-110 as an IV infusion at dose level 2 followed by a maintenance therapy at dose level 2 or 3. |
| Safety Expansion: Cohort 4 | EXPERIMENTAL | Participants with peripheral T-cell lymphoma (PTCL) will receive ARGX-110 as an IV infusion at dose level 2 followed by a maintenance therapy at dose level 2 or 3. |
| Exploratory Efficacy: Cohort 5 | EXPERIMENTAL | Participants with relapsed/refractory CTCL will receive ARGX-110 as an IV infusion followed by a maintenance therapy at dose level 3. |
| ARGX-110 with Azacytidine (AZA) | EXPERIMENTAL | Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m\^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m\^2 BSA, administered SC/IV as per local practice. |
| Experimental: Cohort 2: Cusatuzumab + Venetoclax | EXPERIMENTAL | Participants enrolled in this cohort will receive venetoclax ramp-up to 400 mg orally (as background therapy) starting on Cycle 1 Day 1 and followed by 400 mg daily dosing starting on Cycle 1 Day 4 plus cusatuzumab IV on Day 3 and Day 17 of each 28-day cycle. Cohort 2 will not be enrolled in the US. |
| Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA) | EXPERIMENTAL | Participants enrolled at US sites will receive cusatuzumab 10 mg/kg and potentially escalate to 20 mg/kg IV in combination with azacitidine 75 mg/m\^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). Participants enrolled from ex-US sites will receive cusatuzumab 20 mg/kg and potentially de-escalate to 10 mg/kg IV in combination with azacitidine 75 mg/m\^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). |
| adjuvant monotherapy | EXPERIMENTAL | ARGX-110 5mg/kg once every three weeks for a maximum of 18 cycles |
| metastatic/recurrent monotherapy | EXPERIMENTAL | ARGX-110 5mg/kg once every three weeks until disease progression |
| metastatic/recurrent combination therapy | EXPERIMENTAL | ARGX-110 5mg/kg once every three weeks plus chemotherapy until disease progression. The choice of the chemotherapy agents is limited to: cisplatin, carboplatin, 5-fluorouracil, gemcitabine and paclitaxel. |
| Name | Type | Description |
|---|---|---|
| Azacitidine | DRUG | Azacitidine SC or IV will be administered at a standard dose of 75 mg/m\^2 on days 1-7 of each cycle. |
| Cusatuzumab | DRUG | Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle. |
| ARGX-110 | DRUG | ARGX-110 will be administered as an IV infusion. |
| AZA | DRUG | AZA will be administered subcutaneously/intravenously. |
| Venetoclax | DRUG | Venetoclax will be administered orally and the dose will ramp-up to 400 mg. |
Inclusion Criteria: * Acute myeloid leukemia (AML) according to World Health Organisation (WHO) 2016 criteria and fulfilling all of the following criteria that defines those who are "not candidates for intensive chemotherapy": 1. greater than or equal to (\>=)75 years of age or 2. less than (\...
Cusatuzumab is an investigational monoclonal antibody being studied for the treatment of acute myeloid leukemia (AML). It is also being evaluated in high-risk myelodysplastic syndrome. It is not approved for any indication and remains in clinical development.
Cusatuzumab targets CD70, a protein expressed on leukemic stem cells in acute myeloid leukemia. It is classified as an inhibitor of CD70. By binding CD70, the antibody is designed to interfere with signaling that supports the survival of malignant cells.
Cusatuzumab is being developed by argenx SE, which trades on the Nasdaq under the ticker ARGX. The company is the sponsor of the clinical program evaluating the antibody in acute myeloid leukemia and related blood cancers.
Cusatuzumab is in Phase 2 clinical development. The Phase 2 trial NCT04023526 evaluates cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukemia patients who are not candidates for intensive chemotherapy. Cusatuzumab is investigational and has not been approved by the FDA.
Three trials have studied cusatuzumab. NCT04023526 is a Phase 2 study of cusatuzumab plus azacitidine in newly diagnosed AML. NCT04150887 is a Phase 1 study in AML, and NCT04241549 is a completed Phase 1 study in Japanese participants with AML or high-risk myelodysplastic syndrome.
Yes. Cusatuzumab has been studied in combination with azacitidine, a hypomethylating agent, in patients with newly diagnosed acute myeloid leukemia who are not candidates for intensive chemotherapy. This combination was tested in the Phase 2 trial NCT04023526 and in the Phase 1 trial NCT04241549.