tepoditamab (MCLA-117) / Merus, Gustave Roussy - LARVOL DELTA

MCLA-117 in Acute Myelogenous Leukemia (clinicaltrials.gov) - P1 | N=80 | Terminated | Sponsor: Merus N.V. | Active, not recruiting ➔ Terminated; strategic considerations

Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CLEC12A

ENHANCED LLAMA-DERIVED VHH CLEC12A-CAR-NK CELLS FOR TREATMENT ACUTE MYELOID LEUKEMIA (EBMT 2025) - "The identified VHH domain was incorporated into a second-generation CAR, and its performance was evaluated in vitro and in vivo, in direct comparison to a CAR based on a scFv derived from the therapeutic antibody Tepoditamab... In conclusion, the novel VHH domain AC12VHH4 enables potent tumor cell elimination by CLEC12A-CAR-NK cells, particularly at low E:T ratios, offering a promising strategy for AML immunotherapy. The VHH identified in this study provides a more effective binding domain compared to a scFv derived from a therapeutic antibody for the generation of CLEC12A-CAR NK cells. Current studies focus on evaluating its functionality, as well as its biochemical properties and the in vivo persistence of the IL-15 armored VHH-CLEC12A CAR-NK cells."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CLEC12A • IL15

ENHANCED LLAMA-DERIVED VHH CLEC12A-CAR-NK CELLS FOR TREATMENT ACUTE MYELOID LEUKEMIA (EBMT 2025) - "The identified VHH domain was incorporated into a second-generation CAR, and its performance was evaluated in vitro and in vivo, in direct comparison to a CAR based on a scFv derived from the therapeutic antibody Tepoditamab... In conclusion, the novel VHH domain AC12VHH4 enables potent tumor cell elimination by CLEC12A-CAR-NK cells, particularly at low E:T ratios, offering a promising strategy for AML immunotherapy. The VHH identified in this study provides a more effective binding domain compared to a scFv derived from a therapeutic antibody for the generation of CLEC12A-CAR NK cells. Current studies focus on evaluating its functionality, as well as its biochemical properties and the in vivo persistence of the IL-15 armored VHH-CLEC12A CAR-NK cells."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CLEC12A • IL15

A Novel Asymmetrical Anti-CLL-1×CD3 Bispecific Antibody, ABL602, Induces Potent CLL1-Specific Antitumor Activity with Minimized Sensitization of Pro-Inflammatory Cytokines (ASH 2021) - "ABL602 exhibited higher binding activity to CLL-1-expressing AML cell lines and greater tumor-killing efficacy than 1+1 format BsAb and benchmark antibody MCLA-117 (Merus; CLEC12AxCD3 bispecific antibody). Proportions of bone marrow CD33 + AML blasts diminished in a dose-dependent manner, while CD3 + T cells more infiltrated to the bone marrow. Overall, our results indicate that ABL602, appropriately engineered 2+1 asymmetric BsAb, promotes T-cell activity specifically against CLL1-expressing AML cells and is a promising treatment strategy for AML patients by achieving the desired balance between antitumor activity and safety."

Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • GZMB • IL6 • TNFA

[VIRTUAL] UPDATE FROM THE ONGOING PHASE I MULTINATIONAL STUDY OF MCLA-117, A BISPECIFIC CLEC12A X CD3 T-CELL ENGAGER, IN PATIENTS (PTS) WITH ACUTE MYELOGENOUS LEUKEMIA (AML) (EHA 2020) - "13 pts received tocilizumab which readily reverted CRS. Flow cytometry analyses of cohorts 7-10 show CD69 upregulation in 12 of 14 pts and margination of peripheral T cells in 14 of 18 pts following infusion, both indicative of T-cell activation. Conclusion Preliminary data from the ongoing dose escalation of MCLA-117 show an acceptable safety profile, dose proportional and predictable PK, and early pharmacodynamic and anti-leukemic activity as evident by T-cell activation, margination of peripheral T cells, and reduction in BM blast counts."

Clinical • P1 data • Acute Myelogenous Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology

MCLA-117 in Acute Myelogenous Leukemia (clinicaltrials.gov) - P1; N=62; Active, not recruiting; Sponsor: Merus N.V.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2018 ➔ Jul 2021; Trial primary completion date: Dec 2018 ➔ Jul 2021

Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

MCLA-117: “Clinical activity is observed with ≥ 50% blast reduction in BM, including 1 patient achieving morphological leukemia free state”; Acute myelogenous leukemia (Merus) - EHA 2020: “MCLA-117 is safe and well tolerated with manageable CRS events, following a ramp-up dosing scheme. No MTD reached up to dose of 240 mg”

P1 data • Acute Myelogenous Leukemia • Oncology

Merus announces first quarter 2017 financial results and mid-year operating results (GlobeNewswire) - "With single agent activity established in MBC, the initiation of a Phase 2, open label, multi-center international clinical trial is anticipated in the fourth quarter  of 2017 to evaluate MCLA-128-based combinations in two MBC populations...Decision to support further development path on MCLA-128 in gastric cancer expected in the fourth quarter of 2017...During the second half of 2017, Merus expects to complete the dose escalation phase of its Phase 1 clinical trial evaluating MCLA-117 in patients with AML."

New P1 trial • New P2 trial • Acute Myelogenous Leukemia • Breast Cancer • Gastric Cancer • Hematological Malignancies • Oncology

Merus announces financial results for the third quarter 2018 and provides business update (GlobeNewswire) - "MCLA-117: Biclonics® binding to CD3 and CLEC12A for the treatment of Acute Myeloid Leukemia (AML); Merus plans to provide further guidance on the program upon announcement of the maximum tolerated dose (MTD) and anticipates data readouts for the Phase 1 trial in the second half of 2019."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Merus announces financial results for the first quarter and provides business update (GlobeNewswire) - "Merus continues to enroll patients in the Phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of zenocutuzumab (Zeno) monotherapy in NRG1 gene fusion-positive (NRG1+) solid tumors....The majority of global clinical trial sites for the eNRGy trial are now open and despite slower enrollment and cessation of new recruiting at several clinical trial sites due to COVID-19, Merus remains on track to present data from the Phase 1/2 eNRGy trial by the end of 2020....MCLA-117 Interim Phase 1 data expected in 1H20....Dose escalation is ongoing and MCLA-158 has demonstrated a favorable safety profile with no observed dose limiting toxicities to date. Merus plans to provide an update on the Phase 1 trial by year end."

Enrollment status • P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Merus announces financial results for the second quarter 2018 & mid-year operating results (GlobeNewswire) - "Anticipated 2018 Milestones: we plan to provide an update in the fourth quarter of 2018 on the ovarian, endometrial and non-small cell lung cancer cohorts of the single-agent trial of MCLA-128...The Phase 1/2 study [NCT02912949] evaluating single-agent activity for MCLA-128 in various solid tumor indications is ongoing and Merus will present data on the gastric cohort at ESMO in October 2018...Dose escalation in the Phase 1 clinical trial of MCLA-117 [NCT03038230] is ongoing in Europe and the U.S. A clinical update is planned for fourth quarter of 2018...MCLA-145....continues to progress in IND-enabling studies."

P1 data • P1/2 data • Trial status • Breast Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer

Merus announces the acceptance of six abstracts at upcoming medical conferences and provides program updates (GlobeNewswire) - "Four abstracts regarding zenocutuzumab ('Zeno'), including results from an independent epidemiology study of the prevalence of NRG1 gene fusion-positive ('NRG1+') cancers, will be presented at the American Society for Clinical Oncology ASCO20 Virtual Scientific Program (ASCO)...Abstracts detailing interim data from the Phase 1 MCLA-117 acute myeloid leukemia (AML) trial and an analysis of an extensive, proprietary panel of CD3 bispecific antibodies will be presented at the 25^th European Hematology Association (EHA) Annual Congress Virtual Edition...Merus continues to enroll patients on the Phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of Zeno mootherapy in NRG1+ cancers....Merus has now completed enrollment in two Phase 2 trials of Zeno in metastatic breast cancer."

Clinical data • Enrollment closed • Enrollment open • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

MCLA-117, a CLEC12AxCD3 bispecific antibody targeting a leukaemic stem cell antigen, induces T cell-mediated AML blast lysis. (PubMed, Expert Opin Biol Ther) - "In primary AML patient samples with autologous T cells, MCLA-117 robustly induced AML blast killing (23-98%) at low effector-to-target ratios (1:3-1:97). These findings demonstrate that MCLA-117 efficiently redirects T cells to kill tumour cells while sparing the potential of the bone marrow to develop the full hematological compartment and support further clinical evaluation as a potentially potent treatment option for AML."

Journal

MCLA-117: Protection of patent related to dosage regimes and methods of treatment until December 20, 2039 (Merus) - Annual Report 2019

Patent

Merus announces financial results for the fourth quarter and full year 2019 and provides business update (GlobeNewswire) - P1, N=120; NCT03526835; "MCLA-117 (CLEC12A x CD3 Biclonics®): Acute Myeloid Leukemia (AML) – Initial Phase 1 data expected in 1H20; MCLA-158 (Lgr5 x EGFR Biclonics®): Solid Tumors – Phase 1 trial progressing at higher dose cohorts...The Phase 1 protocol was amended to allow for the exploration of higher dose cohorts. Dose escalation is ongoing and as of year-end, MCLA-158 has demonstrated a favorable safety profile with no observed dose limiting toxicities."

Clinical protocol • P1 data • Trial status

Merus announces financial results for the third quarter 2019 and provides business update (GlobeNewswire) - "MCLA-128 (HER3 x HER2 Biclonics®): Early clinical activity presented in patients with pancreatic and lung cancers harboring NRG1 fusions; more mature data expected to be presented at a medical conference by end of 2020....In the Phase 2 Metastatic Breast Cancer trial, in patients enrolled as of August 31, 2019, Merus conducted an unplanned interim efficacy analysis with a data cut-off of October 23, 2019. The company expects to present mature results, including the primary endpoint of clinical benefit rate at 24 weeks for both cohorts at a medical conference in 2020....MCLA-117 (CLEC12A x CD3 Biclonics®): Expect to present initial Phase 1 data at a medical conference 1H 2020...MCLA-158 (Lgr5 x EGFR Biclonics®): Initial safety data from Phase 1 trial expected at end of 2019, further guidance in 2020 [solid tumor]."

Clinical data • P2 data

MCLA-117: Initial data from P1 trial (NCT03038230) for AML H1 2020 (Merus) - Corporate Presentation

P1 data

DARTS, Bites and ADCs for the Treatment of AML and for Conditioning for Allogeneic Stem Cell Transplantation (SOHO 2019) - "These include JNJ-63709178; (target: CD123; trial suspended), XmAb14045; (target: CD123), Flotetuzumab/DART; (target: CD123) as well as others focused on CD33 (AMG330, AMG673, AMV564, GEM333) and CLL-1 (MCLA-117). Additional correlative studies will be presented for this and other AML bispecifics currently being tested by our and other groups in the clinic. Finally, we will present data on the use of ADCs for the treatment of AML in vitro and for conditioning for stem cell transplantation within and across MHC barriers using mouse preclinical transplant models."

IO Biomarker

Merus Announces Financial Results for the Second Quarter 2019 and Provides Business Update (GlobeNewswire, Merus N.V.) - “Patient enrollment for our MCLA-158 and MCLA-145 Phase 1 trials is on track. Importantly, we amended the MCLA-117 T-cell engager trial to allow us to explore higher doses, and we re-focused our MCLA-128 Phase 1/2 monotherapy trial on a subpopulation of patients with solid tumors harboring NRG1 gene fusions. We plan to report on our Phase 2 MCLA-128 MBC trial in the fourth quarter....Merus amended the MCLA-117 protocol to allow for the exploration of higher doses. The Phase 1 trial initiated at a low dose level based on the potent nature of T-cell engagers. Due to this amendment and continued dose escalation, Merus now plans to present initial data at a medical conference in the first half of 2020."

Clinical • Commercial • New trial

Merus Announces Financial Results for the First Quarter 2019 and Provides Business Update (GlobeNewswire, Merus N.V.) - "The Phase 2 clinical trial evaluating MCLA-128 in combination treatments in two metastatic breast cancer ('MBC') populations continues to enroll patients in the U.S. and Europe...Merus plans to provide an update on the Phase 2 MBC trial in the second half of 2019...The single agent Phase 1/2 trial in solid tumors is ongoing in the non-small-cell lung cancer ('NSCLC') and gastric cancer and gastroesophageal junction cancer ('GC/GEJ') cohorts, with the GC/GEJ cohort enrollment completed. In the NSCLC cohort, an update is expected in the second half of 2019...The Phase 1 clinical trial for MCLA-117 is progressing and preliminary anti-tumor activity has been observed...Merus anticipates initial data for the Phase 1 trial in the second half of 2019...MCLA-145 (CD137 x PD-L1 Biclonics®): First patient treated in Phase 1 clinical trial"

Clinical data • Enrollment status • Preclinical • Trial status

Merus Announces Financial Results for the Full Year 2018 and Provides Business Update (GlobeNewswire, Merus N.V.) - "Merus plans to provide an update on the Phase 2 MBC trial [of MCLA-128] in the second half of 2019...Merus anticipates initial data for the Phase 1 trial [of MCLA-117] in the second half of 2019 and plans to provide further guidance on the program upon announcement of the maximum tolerated dose...The dose escalation of the Phase 1 clinical trial of MCLA-158 in patients with solid tumors is ongoing. Emerging data for the Phase 1 trial is expected at the end of 2019."

Clinical data