lacnotuzumab (MCS110) / Novartis - LARVOL DELTA

MCS110 With BRAF/MEK Inhibition in Patients With Melanoma (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: Dana-Farber Cancer Institute | Active, not recruiting ➔ Completed | N=43 ➔ 6 | Trial completion date: Sep 2025 ➔ Sep 2023 | Trial primary completion date: Sep 2024 ➔ Sep 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies. (PubMed, J Immunother Precis Oncol) - P1/2 | "However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored."

Combination therapy • Journal • Metastases • P1/2 data • Breast Cancer • Endocrine Disorders • Endometrial Cancer • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CSF1

Updates on the Treatment of Tenosynovial Giant Cell Tumor. (PubMed, Hematol Oncol Stem Cell Ther) - "Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab."

Journal • Review • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition. (PubMed, Invest New Drugs) - "MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration."

IO biomarker • Journal • P1/2 data • Immune Modulation • Melanoma • Oncology • Solid Tumor • CSF1

Phase Ib/II study of lacnotuzumab (MCS110) combined with spartalizumab (PDR001) in patients (pts) with advanced tumors. (ASCO 2018) - P1/2; "Lacnotuzumab with spartalizumab was well tolerated overall. Preliminary antitumor activity, notably in the PC cohort, was observed. Ongoing studies are evaluating this combination."

Clinical • IO biomarker • P1/2 data • PD(L)-1 Biomarker • Hormone Receptor Breast Cancer • Melanoma • Triple Negative Breast Cancer

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; This was a sponsor decision and was not a consequence of any safety concern

IO biomarker • Trial termination • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2022 ➔ Feb 2023 | Trial primary completion date: Oct 2022 ➔ Feb 2023

IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2022 ➔ Oct 2022 | Trial primary completion date: Jun 2022 ➔ Oct 2022

IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=220 ➔ 64 | Trial completion date: Jan 2022 ➔ Jun 2022 | Trial primary completion date: Jan 2022 ➔ Jun 2022

Enrollment change • Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

MCS110 With BRAF/MEK Inhibition in Patients With Melanoma (clinicaltrials.gov) - P1/2; N=43; Active, not recruiting; Sponsor: Dana-Farber Cancer Institute; Trial primary completion date: Sep 2021 ➔ Sep 2024

Clinical • Trial primary completion date • Melanoma • Oncology • Solid Tumor • MRI

A Randomized Phase II Study of Anti-CSF-1 Monoclonal Antibody Lacnotuzumab (MCS110) Combined with Gemcitabine and Carboplatin in Advanced Triple Negative Breast Cancer. (PubMed, Clin Cancer Res) - "Despite successful target engagement and anticipated pharmacokinetic profile, lacnotuzumab+gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this manuscript would be informative for future studies testing agents targeting the CSF-1-CSF-1R pathway in TNBC."

Clinical • Journal • P2 data • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CSF1 • CSF1R

Phase Ib/II study of lacnotuzumab (MCS110) combined with spartalizumab (PDR001) in patients (pts) with advanced tumors. (ASCO 2018) - P1/2; "Lacnotuzumab with spartalizumab was well tolerated overall. Preliminary antitumor activity, notably in the PC cohort, was observed. Ongoing studies are evaluating this combination."

Clinical • IO biomarker • P1/2 data • PD(L)-1 Biomarker • Hormone Receptor Breast Cancer • Melanoma • Triple Negative Breast Cancer

[VIRTUAL] On-target peripheral and tumor immune microenvironment modulation in patients treated with lacnotuzumab (anti-CSF1, MCS110) + spartalizumab (AACR 2021) - "Flow cytometric, circulating total CSF1 in plasma and gene expression profiling results demonstrated that targeting CSF-1 with lacnotuzumab in the periphery and tumor microenvironment leads to decrease in monocytes and reduced expression of macrophage associated genes in patients with advanced cancers. Unfortunately, in the heavily pretreated patient populations studied in this trial, only a limited clinical efficacy was demonstrated."

Clinical • IO biomarker • Late-breaking abstract • Breast Cancer • Endometrial Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CSF1 • CSF1R

[VIRTUAL] M-CSF secreted factor as a therapeutic target in BRAFV600E acquired resistant melanoma (EADO-WCM 2021) - " We obtained conditioned medium (CM) from cultured BRAFV600E-mutant Vemurafenib sensitive (Vem-S) and paired resistant (Vem-R) melanoma cell lines...Human melanoma xenograft mice model (SCID) was performed and mice were treated with Vem (50 mg/kg), M-CSF mAb (Lacnotuzumab) (4 mg/kg), and/or Chloroquine (30 mg/kg) and combined treatments... We have described for the first time an increase of M-CSF secretion in resistant BRAFV600E-mutant melanoma cells and its promotion to induce BRAFi-resistant phenotype. Antibodies against M-CSF may offer a new promising therapy to deal with resistant melanoma patients."

Melanoma • Oncology • Skin Cancer • Solid Tumor • CSF1

MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer (clinicaltrials.gov) - P1; N=27; Not yet recruiting; Sponsor: Washington University School of Medicine; Trial completion date: Nov 2020 ➔ Feb 2021; Initiation date: Jun 2018 ➔ Sep 2018; Trial primary completion date: Jul 2019 ➔ Oct 2019

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • ER • HER-2

MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: Washington University School of Medicine; N=27 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • ER • HER-2

MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer (clinicaltrials.gov) - P1; N=27; Not yet recruiting; Sponsor: Washington University School of Medicine; Trial completion date: Jul 2020 ➔ Sep 2020; Initiation date: Feb 2018 ➔ Apr 2018; Trial primary completion date: Mar 2019 ➔ May 2019

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • ER • HER-2

MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer (clinicaltrials.gov) - P1; N=27; Not yet recruiting; Sponsor: Washington University School of Medicine

Clinical • New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • ER • HER-2

MCS110 With BRAF/MEK Inhibition in Patients With Melanoma (clinicaltrials.gov) - P1/2; N=43; Active, not recruiting; Sponsor: Dana-Farber Cancer Institute; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Melanoma • Oncology • Solid Tumor

Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2; N=50; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed; Trial completion date: Jul 2020 ➔ Mar 2020; Trial primary completion date: Jul 2020 ➔ Mar 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

Phase Ib/II Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1/2; N=141; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Breast Cancer • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer

Newly added product (clinicaltrials.gov) - P2, Gastric cancer

Pipeline update • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2; N=50; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Mar 2020 ➔ Jul 2020; Trial primary completion date: Dec 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1; N=220; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Oct 2020 ➔ Jan 2022; Trial primary completion date: Oct 2020 ➔ Jan 2022

Clinical • IO Biomarker • Trial completion date • Trial primary completion date • CD8 • ER • HER-2 • PD-L1

MCS110 With BRAF/MEK Inhibition in Patients With Melanoma (clinicaltrials.gov) - P1/2; N=43; Recruiting; Sponsor: Dana-Farber Cancer Institute; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open