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DRUG:

modakafusp alfa (TAK-573)

i
Other names: TEV-48573, TEV 48573, TAK-573, TAK573, TAK 573
Associations
Company:
Takeda
Drug class:
CD38 inhibitor, IFNα stimulant
Associations
2ms
iinnovate-3: A Study of Modakafusp Alfa Together With Daratumumab Adults With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
P1/2, N=15, Completed, Takeda | Active, not recruiting --> Completed | N=58 --> 15 | Trial completion date: Mar 2025 --> May 2024 | Trial primary completion date: Mar 2025 --> May 2024
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
Darzalex Faspro (daratumumab and hyaluronidase-fihj) • modakafusp alfa (TAK-573)
4ms
iinnovate-2: A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
P1, N=15, Completed, Takeda | Active, not recruiting --> Completed | N=120 --> 15
Trial completion • Enrollment change • Combination therapy
|
lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
5ms
iinnovate-2: A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
P1, N=120, Active, not recruiting, Takeda | Trial completion date: Jan 2028 --> Jun 2024 | Trial primary completion date: Jul 2025 --> Jan 2024
Trial completion date • Trial primary completion date • Combination therapy
|
lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
10ms
New Therapies on the Horizon for Relapsed Refractory Multiple Myeloma. (PubMed, Hematol Oncol Clin North Am)
Venetoclax is a B-cell lymphoma 2 (Bcl-2) inhibitor with activity in patients with t(11;14) and/or Bcl-2 expression. Iberdomide and mezigdomide are cereblon E3 ligase modulators with higher potency, immunomodulatory, and antiproliferative activity compared with lenalidomide and pomalidomide...Modakafusp alfa is an immunocytokine that targets interferons to CD38+ cells. It has demonstrated single agent activity in relapsed/refractory MM in the phase 1 setting.
Review • Journal • IO biomarker
|
CD38 (CD38 Molecule) • CRBN (Cereblon)
|
Chr t(11;14) • BCL2 expression
|
Venclexta (venetoclax) • lenalidomide • pomalidomide • iberdomide (CC-220) • mezigdomide (CC-92480) • modakafusp alfa (TAK-573)
11ms
iinnovate-1: A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
P1/2, N=336, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting
Enrollment closed
|
modakafusp alfa (TAK-573)
11ms
Enrollment closed • Combination therapy
|
Darzalex Faspro (daratumumab and hyaluronidase-fihj) • modakafusp alfa (TAK-573)
11ms
iinnovate-2: A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
P1, N=120, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy
|
lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
11ms
A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=45, Completed, Takeda | Recruiting --> Completed | Phase classification: P1b/2 --> P1/2 | N=114 --> 45
Trial completion • Phase classification • Enrollment change
|
BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
BRAF V600E • BRAF V600
|
Keytruda (pembrolizumab) • modakafusp alfa (TAK-573)
almost1year
Phase classification • Combination therapy
|
lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
1year
Modakafusp Alfa Demonstrates Type I Interferon-Mediated Innate and Adaptive Immune Enhancement in a Phase 1/2 Study in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM) (ASH 2023)
Follow-up analyses of the correlation of biomarkers with clinical response are in progress and will be presented. Further clinical trials are underway (iinnovate-2, NCT05556616; iinnovate-3, NCT05590377) to evaluate moda's novel immune activating mechanism in combination with standard of care anti-myeloma therapies.
Clinical • P1/2 data • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD69 (CD69 Molecule) • CD68 (CD68 Molecule) • GZMB (Granzyme B) • FOXP3 (Forkhead Box P3) • CD40LG (CD40 ligand) • IFNA1 (Interferon Alpha 1) • CD86 (CD86 Molecule)
|
CD38 expression
|
modakafusp alfa (TAK-573)
1year
A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1b/2, N=114, Recruiting, Takeda | Trial completion date: Sep 2023 --> Jan 2024 | Trial primary completion date: Sep 2023 --> Jan 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
BRAF V600E • BRAF V600
|
Keytruda (pembrolizumab) • modakafusp alfa (TAK-573)
1year
Atypical Hemolytic Uremic Syndrome (aHUS)/TMA in Genetically Predisposed Patients Treated with a Novel Agent for Relapsed/Refractory Multiple Myeloma (KIDNEY WEEK 2023)
Both patients had hemodialysis & eculizumab while inpatient & are continuing on hemodialysis on an outpatient basis. Both patients were recently started on carfilzomib & modakafusp alfa, a relatively new phase I/II clinical trial. Case reports of aHUS/TMA from carfilzomib do exist, however. We conclude that it is reasonable to perform genetic testing prior to initiating treatment with modakafusp alfa +/- carfilzomib, to mitigate the risk of aHUS/TMA as seen in our two patients.
Clinical • IO biomarker
|
CD38 (CD38 Molecule) • IFNA1 (Interferon Alpha 1)
|
LDH elevation
|
carfilzomib • modakafusp alfa (TAK-573)
1year
Rationale and design of three ongoing phase 1/2 trials of modakafusp alfa, an innate immunity enhancer, in patients with multiple myeloma: The iinnovate clinical development program (IMW 2023)
As moda and daratumumab (dara) do not bind to the same epitope, they may have complementary mechanisms of action; furthermore, moda has been shown to increase CD38 expression on immune and MM cells. In the phase 2 iinnovate-1 extension study (NCT03215030), pts are randomized to receive moda 120 mg or 240 mg every four weeks to define the single-agent dose with the optimal benefit/risk profile in pts with ≥3 prior lines of therapy (LoT) who are at least triple-class refractory (to an IMiD, a PI, and an anti-CD38 mAb)...In group 1, moda is combined with lenalidomide (len) as post-transplant maintenance therapy... The ongoing iinnovate-1-2-3 studies are assessing the optimal dose of moda as a single agent and as part of doublet and triplet combinations with SOC agents for different MM pt populations, including those with high unmet medical needs.
Clinical • P1/2 data • IO biomarker
|
IFNA1 (Interferon Alpha 1)
|
CD38 expression
|
lenalidomide • Darzalex (daratumumab) • modakafusp alfa (TAK-573)
over1year
iinnovate-1: A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
P1/2, N=336, Recruiting, Takeda | Trial completion date: Apr 2025 --> Sep 2024 | Trial primary completion date: May 2023 --> Mar 2024
Trial completion date • Trial primary completion date
|
modakafusp alfa (TAK-573)
over1year
THE MODAKAFUSP ALFA IINNOVATE CLINICAL DEVELOPMENT PROGRAM: RATIONALE AND DESIGN OF 3 PHASE 1/2 TRIALS OF AN INNATE IMMUNITY ENHANCER FOR MULTIPLE MYELOMA (MM) (EHA 2023)
iinnovate-3 (NCT05590377) is a phase 1/2a study to evaluate the safety, tolerability, and preliminary efficacy of moda in combination with dara SC...Two dose levels of moda in combination with dara will be selected for phase 2a optimal dose finding in pts who have received 1–3 prior lines and are refractory to lenalidomide and sensitive (non-refractory) or naïve to an anti-CD38 mAb... The iinnovate-1-2-3 studies plan to determine the optimal dose of moda as a single agent and in doublet and triplet combinations with SOC agents for different MM pt populations, including pts with the highest unmet medical needs. Interferon alpha, Multiple myeloma, Innate Immunity, Cancer immunotherapy
Clinical • P1/2 data • IO biomarker
|
IFNA1 (Interferon Alpha 1)
|
CD38 expression
|
lenalidomide • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • modakafusp alfa (TAK-573)
2years
A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
P1b | N=144 | Recruiting | Sponsor: Takeda | Not yet recruiting --> Recruiting
Combination therapy • Enrollment open
|
lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
2years
Final Results from the First-in-Human Phase 1/2 Study of Modakafusp Alfa, an Immune-Targeting Attenuated Cytokine, in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2022)
As dexamethasone (dex) is part of standard of care in MM, but could counteract the immune activation elicited by modakafusp, additional cohorts at 0.4 mg/kg Q3W and 1.5 mg/kg Q4W in combination with 40 mg dex QW were opened. Conclusions Modakafusp alfa has a novel mechanism of action, a manageable safety profile, and encouraging anti-myeloma activity at 1.5 mg/kg Q4W, independent of peripheral blood immune cell CD38 expression. A randomized phase 2 study to compare fixed-dose levels of 120 and 240 mg (equivalent to 1.5 and 3.0 mg/kg) Q4W and to define the single-agent dose with the optimal benefit/risk profile is currently enrolling.
P1/2 data • Clinical • IO biomarker
|
IFNA1 (Interferon Alpha 1)
|
CD38 expression
|
clonoSEQ
|
dexamethasone • modakafusp alfa (TAK-573)
2years
Modakafusp Alfa (TAK-573), a Novel CD38-Targeting Attenuated Interferon-Alpha Immunocytokine, Kills MM Cells Via NK Cell Activation (ASH 2022)
This important MoA also results in improved efficacy of daratumumab or elotuzumab in short-term cytotoxicity assays. Our findings warrant clinical investigation of combining modakafusp alfa with NK cell-exploiting immunotherapies.
IO biomarker
|
CD69 (CD69 Molecule) • SLAMF7 (SLAM Family Member 7)
|
CD38 expression • CD38 positive
|
Darzalex (daratumumab) • Empliciti (elotuzumab) • modakafusp alfa (TAK-573)
2years
Combination therapy • New P1 trial
|
lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
over2years
A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
P1/2 | N=336 | Recruiting | Sponsor: Takeda | N=151 --> 336 | Trial completion date: Feb 2022 --> Apr 2025 | Trial primary completion date: Feb 2022 --> May 2023
Trial completion date • Trial primary completion date • Enrollment change
|
modakafusp alfa (TAK-573)
3years
Modakafusp Alfa (TAK-573), an Immunocytokine, Shows Clinical Activity in Patients with Relapsed/Refractory Multiple Myeloma; Updated Results from a First-in-Human Phase 1 Study (ASH 2021)
Furthermore, modakafusp alfa binds to a different epitope on CD38 than the currently approved anti-CD38 therapeutic mAbs, daratumumab and isatuximab. Modakafusp alfa (TAK-573) is a novel candidate for the treatment of RRMM, which has shown promising anti-myeloma activity in heavily pretreated pts, including anti-CD38 mAb-refractory pts and those who have received an anti-CD38 mAb in their most recent line of treatment. A Q4W dosing schedule of modakafusp alfa is feasible and the optimal dose and potential combinations are being explored.
Clinical • P1 data • IO biomarker
|
IFNA1 (Interferon Alpha 1)
|
CD38 expression
|
Darzalex (daratumumab) • Sarclisa (isatuximab-irfc) • modakafusp alfa (TAK-573)
over3years
A Study of TAK-573 Given by Itself and Together With Pembrolizumab in Adults With Metastatic Solid Tumors (clinicaltrials.gov)
P1b/2; N=114; Recruiting; Sponsor: Takeda; Phase classification: P1 --> P1b/2; N=86 --> 114
Combination therapy • Enrollment change • Phase classification • Clinical
|
BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
BRAF V600E • BRAF V600
|
Keytruda (pembrolizumab) • modakafusp alfa (TAK-573)
4years
[VIRTUAL] TAK-573, an Anti-CD38/Attenuated Ifnα Fusion Protein, Has Clinical Activity and Modulates the Ifnα Receptor (IFNAR) Pathway in Patients with Relapsed/Refractory Multiple Myeloma (ASH 2020)
TAK-573 binds to a site on CD38 that is distinct from the binding sites of currently available therapeutic antibodies, and therefore does not compete for binding with daratumumab or isatuximab. TAK-573 is a clinically and pharmacologically active molecule that mediates IFNAR pathway modulation and leads to myeloma responses. Additional biomarker data is being collected to further refine the MOA, which will inform the recommended phase 2 dose, optimal schedule of administration, and rational development of TAK-573.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
|
CD38 positive
|
Darzalex (daratumumab) • Sarclisa (isatuximab-irfc) • modakafusp alfa (TAK-573)
4years
[VIRTUAL] TAK-573, an anti-CD38–attenuated interferon alpha (IFNα) fusion protein (Attenukine™), has demonstrated IFNα receptor (IFNAR) pathway modulation in patients with relapsed/refractory multiple myeloma (SITC 2020)
Proposed Mechanism of Action of TAK-573 Conclusions These preliminary biomarker data indicate that TAK-573 is a pharmacologically active molecule that mediates its effect through IFNAR pathway modulation. Additional data are being collected to further refine the mechanism of action (Image 1), which will inform the recommended phase 2 dose and optimal schedule of administration for the development of TAK-573.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • GZMB (Granzyme B) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
|
CD38 expression
|
modakafusp alfa (TAK-573)
4years
[VIRTUAL] TAK-573, an anti-CD38–attenuated interferon alpha (IFNα) fusion protein (Attenukine™), has demonstrated IFNα receptor (IFNAR) pathway modulation in patients with relapsed/refractory multiple myeloma (SITC 2020)
Proposed Mechanism of Action of TAK-573 Conclusions These preliminary biomarker data indicate that TAK-573 is a pharmacologically active molecule that mediates its effect through IFNAR pathway modulation. Additional data are being collected to further refine the mechanism of action (Image 1), which will inform the recommended phase 2 dose and optimal schedule of administration for the development of TAK-573.
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • GZMB (Granzyme B) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
|
CD38 expression
|
modakafusp alfa (TAK-573)
over4years
A Study of TAK-573 Given by Itself and Together With Pembrolizumab in Adults With Metastatic Solid Tumors (clinicaltrials.gov)
P1, N=86, Recruiting, Millennium Pharmaceuticals, Inc. | Active, not recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy • IO biomarker
|
BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
BRAF V600E • BRAF V600
|
Keytruda (pembrolizumab) • modakafusp alfa (TAK-573)
over4years
[VIRTUAL] A murine reactive version of TAK-573 (anti-CD38 attenuated IFNα fusion protein) shows immunomodulatory and antitumor activity, alone and in combination with standard-of-care agents, in IFNa-insensitive, immunocompetent murine multiple myeloma tumor models (AACR-II 2020)
Administration of mCD38-mATT induced broad immunomodulation and antitumor responses, alone and in combination with SOC agents in immunocompetent mouse models, highlighting the impact of this agent on CD38+ cells, both tumor and immune. These results support further investigation of combination therapies in the ongoing clinical evaluation of TAK-573 in a Phase 1 trial in patients with relapsed refractory MM.
Preclinical • Combination therapy • IO biomarker
|
CD38 (CD38 Molecule)
|
modakafusp alfa (TAK-573)
over4years
A Study of TAK-573 Given by Itself and Together With Pembrolizumab in Adults With Metastatic Solid Tumors (clinicaltrials.gov)
P1, N=105, Active, not recruiting, Millennium Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting
Clinical • Enrollment closed • Combination therapy • IO biomarker
|
BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
|
BRAF V600E • BRAF V600
|
Keytruda (pembrolizumab) • modakafusp alfa (TAK-573)