Open-label, two parallel arm, multicenter, Phase 1 dose-escalation study to evaluate the safety and tolerability of OMTX705, both as monotherapy or in combination with pembrolizumab (Part 1) or tislelizumab (Part 2) in the treatment of patients with advanced or metastatic cancer in whom there is no available standard therapeutic option.
Male and female patients aged 18 years and older.
Part 1 monotherapy and combination: Patients with histologically confirmed advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors that have no standard therapeutic option with a proven clinical benefit, or are intolerant to these therapies with any of the following selected tumor histologies: PDAC, gastric cancer (including gastroesophageal junction tumors), head and neck squamous-cell carcinoma (HNSCC), esophageal cancer, NSCLC, high grade serous ovarian cancer, primary peritoneal cancer, mesothelioma, BC, CRC, and FAP positive leiomyosarcoma or other FAP-positive sarcomas (with sponsor's approval). Patients with other tumor histologies may be enrolled with explicit sponsor's approval.
SARC1 cohort: patients with locally advanced or metastatic FAP-positive sarcomas that have no standard therapeutic option with a proven clinical benefit or are intolerant to these therapies. FAP-positive is defined as expression of FAP with an H-score ≥40 or 2+/3+ in a tumor biopsy that can be either archival or fresh. FAP positivity will be considered exclusively on sarcoma cells and not in surrounding fibroblasts or other stromal cells. FAP measurement will be done in a central laboratory provided by the sponsor during the screening period (in countries where this is permitted). Alternatively, eligible patients may have had FAP quantified locally before enrolling the trial as part of the previous care of the patient. In the latter case, FAP will be re-quantified retrospectively in a central lab designated by the sponsor.
PDAC_low and_high cohorts: patients with metastatic PDAC who have received at least two and no more than four previous lines of systemic treatment for metastatic disease. If the patient received neoadjuvant/adjuvant therapy and recurred <6 months after the last dose, this line will be counted as the first line for the metastatic disease.
Treatment with systemic anticancer treatments, investigational products, or major surgery within four weeks before the first dose of study drug or five half-lives, whichever is shorter. Subjects should have recovered from previous treatment toxicity to Grade 1, baseline (except alopecia). Patients with endocrinopathies should have the replacement treatment in stable dosing.
History of uncontrolled brain metastasis. Subjects with brain metastases are allowed if they are previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery and have new brain imaging confirming that brain metastasis are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or CT and considered controlled with <10 mg/day of prednisone-equivalent at the time of receiving the first dose of OMTX705. For asymptomatic subjects, screening brain imaging is not required.
Patient has received extended field radiotherapy ≤four weeks before the start of treatment (≤one week for limited field radiation for palliation), and who has not recovered to Grade 1 or better from related side effects of such therapy (except for alopecia).
Active infection requiring parenteral or oral antibiotics. Antibiotics given for prophylaxis are allowed. They are also allowed for minor localized infections like cystitis, tonsilitis or localized skin infections.
Parallel
OMTX705
DrugThe investigational product is OMTX705 administered as monotherapy at different escalation doses.
Pembrolizumab
DrugPembrolizumab at 200 mg administered in combination with different escalation doses of OMTX705.
OMTX705
DrugThe investigational product is OMTX705 administered as monotherapy at 10 mg/kg
OMTX705
DrugThe investigational product is OMTX705 administered as monotherapy at 15 mg/kg
OMTX705
DrugThe investigational product is OMTX705 administered as monotherapy at 7.5 mg/kg
Tislelizumab (BGB-A317)
DrugTislelizumab at 200 mg is administered in combination with OMTX705
OMTX705
DrugThe investigational product is OMTX administered at 4.0 mg/kg
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Treatment groupsSee each treatment group below.
Safety evaluation of OMTX705
Frequency by grade of treatment-emergent adverse events (TEAEs).
Evaluation of the preliminary signs of antitumor activity of OMTX705 as monotherapy and in combination with pembrolizumab
By assessing the objective response rate (ORR) \[complete response (CR) + partial response (PR)\] per the Response Evaluation Criteria in Solid Tumors scale version 1.1 (RECIST 1.1)
Evaluation of the OMTX705 Pharmacokinetics
By assessing plasma drug concentrations of OMTX705 as monotherapy and with pembrolizumab/tislelizumab, with Ultra-High-Performance Liquid Chromatography (UPLC-MS/MS) and immunosorbent assay (ELISA) methods
Evaluation of OMTX705 Immunogenicity
By quantifying the formation of anti-drug antibodies (ADAs) with Meso Scale Discovery (MSD) immunoassay method.
Evaluation of standard cancer serum biomarkers
By measuring the change in circulating cancer blood biomarkers prior and after using OMTX705 as monotherapy and in combination with pembrolizumab/tislelizumab
Evaluation of OMTX705 biomarkers
By measuring the changes in circulating OMTX705 biomarkers prior and after using OMTX705 as monotherapy and in combination with pembrolizumab/tislelizumab
Evaluation of OMTX705 payload metabolites
By quantifying OMTX705 payload TAM470 metabolites prior and after using OMTX705 as monotherapy and in combination with pembrolizumab/tislelizumab.
Evaluation of QTc prolongation
By performing electrocardiography (ECG) pre and at the end of the OMTX705 infusion as monotherapy and in combination with pembrolizumab/tislelizumab..
Click on the lead sponsor to view all of their trials.
Oncomatryx Biopharma S.L.
Lead sponsor
Centro de Investigación del Cáncer Universidad de Salamanca
Collaborator
CTI Laboratory Services Spain
Collaborator
Anapharm Bioanalytics
Collaborator
Certara
Collaborator
Biotrial
Collaborator
Alcura Health España SA
Collaborator
Clinigen, Inc.
Collaborator
Evidenze CRO
Collaborator
TFS Health Science
Collaborator
HistoOne
Collaborator
Opthimapharm
Collaborator
