Advanced Solid Tumor Clinical Trial
Official title:
Phase 1 Dose-escalation Trial of OMTX705, an Anti-fibroblast Activation Protein Antibody-drug Conjugate, as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
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 in the treatment of patients with advanced or metastatic cancer in whom there is no available standard therapeutic option.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | October 2024 |
Est. primary completion date | October 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Male and female patient aged 18 years and older. 2. Part 1 and 2, 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 the following selected tumor histologies: pancreatic ductal adenocarcinoma (PDAC), gastric cancer (including gastroesophageal junction tumors), head and neck squamous-cell carcinoma (HNSCC), esophageal cancer, non-small cell lung cancer (NSCLC), high grade serious ovarian cancer (HGSOC), breast cancer (BC), colorectal cancer (CRC), and leiomyosarcoma. 3. Subjects with tumors with actionable mutations should have progress to all approved targeted therapies or have them contraindicated. 4. Measurable disease by RECIST 1.1 on CT, PET/CT or MRI scan. 5. ECOG performance status 0-1 6. Serum albumin =3.0 g/dL 7. Adequate bone marrow, hepatic and renal function: 1. Total bilirubin =1.5 times upper limit of normal (ULN). 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times ULN, (if liver metastases are present, then =5 times ULN is allowed). 3. For Dose escalation Phase: Estimated creatinine clearance (CrCL) using the Cockcroft-Gault formula =60 mL/minute. Patients with calculated CrCL <60 mL/min can be enrolled if measured CrCL is =60 mL/min. 4. In the expansion phase CrCL should be =30 mL/min. 5. Hemoglobin =9 g/dL (whole or partial blood transfusions not allowed in the 2 previous weeks). 6. Absolute neutrophil count (ANC) =1.5 x 109/L (growth factors like G-CSF are not allowed in the 2 previous weeks). 7. Platelet count =75 x 109/L (platelet in the 2 previous weeks transfusions not allowed) 8. Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP must be willing to adhere to contraceptive requirements as detailed in the protocol from at least 1 month prior to study entry to at least 4 months after the last dose of study treatment. 9. Suitable venous access for safe drug administration and the study-required drug concentration and pharmacodynamic sampling. Exclusion Criteria: 1. Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter. Subjects should have recovered from previous treatment toxicity to grade 1, baseline (except alopecia and peripheral neuropathy). Patients with endocrinopathies should have the replacement treatment in stable dosing. 2. History of uncontrolled brain metastasis. For asymptomatic subjects, screening brain imaging is not required. 3. Subject has received extended field radiotherapy =4 weeks before the start of treatment (=1 weeks 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). 4. Active infection requiring parenteral or oral antibiotics. 5. Evidence of serious uncontrolled medical disorder that, in the opinion of the investigator or medical monitor, makes it unwise for the subject to participate in the study or that might jeopardize compliance with the protocol. 6. Drainage of ascitic or pleural fluid 2 or more times in the 4 weeks prior to the first dose of study drug or permanent drain in place for ascites or pleural effusion symptom management. 7. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent. 8. Clinical evidence of an active second invasive malignancy with the exception of stable prostate cancer on watchful waiting, in situ cervical cancer, breast ductal carcinoma in situ or localized non-melanoma skin cancers. 9. Uncontrolled or significant cardiovascular disease defined as NYHA classification III or IV. 10. Baseline QTc (using the Fridericia correction calculation) > 470 msec. 11. Combination with pembrolizumab only: history of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day). 12. Combination with pembrolizumab only: Subjects who, according to the currently approved Keytruda® (pembrolizumab) USPI/SmPC, had, with a previous checkpoint inhibitor (approved or investigational) treatment, an immune-related adverse event (irAE) for which permanent discontinuation is mandated (any grade 4 event and grade 3 events of pneumonitis, hepatitis, and nephritis). Also, subjects without formal contraindication due to previous irAE are not eligible if the AE has not resolved to grade 1 or better and/or still requires steroids (>10 mg of prednisone equivalent per day) for ongoing management. 13. Combination with pembrolizumab only: patients with a history of pneumonitis/interstitial lung disease, patients who received live vaccines within 30 days of enrollment, and patients who discontinued prior immune checkpoint inhibitors due to Grade 2 myocarditis are excluded from enrollment into pembrolizumab-containing cohorts. 14. Known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load. 15. Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must meet the following criteria: 1. have CD4+ T-cell (CD4+) counts =350 cells/µL. 2. have not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the trial. 3. should be on established antiretroviral therapy for at least 4 weeks. 4. have an HIV viral load less than 400 copies/mL prior to enrollment. 5. known history of any other relevant congenital or acquired immunodeficiency other than HIV infection. 16. Known or suspected allergy to study treatment or related products, and specifically patients with a prior history of life-threatening reaction to polysorbate 20. 17. Women who are pregnant or breastfeeding or trying to become pregnant. 18. Male patients wishing fathering children, planning for future sperm banking, or expressing concerns about sterility. 19. Patients requiring the concomitant administration of medications that are strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9, 2B6, and 2C19. In case they are taking any of these drugs, they should be stopped at least 14 days prior to first dose. |
Country | Name | City | State |
---|---|---|---|
Spain | Hospital Universitari Vall d'Hebron | Barcelona | |
Spain | ICO L'Hospitalet | L'Hospitalet de Llobregat | Barcelona |
Spain | Hospital 12 Octubre | Madrid | |
Spain | Hospital MD Anderson | Madrid | |
Spain | Clínica Universitaria de Navarra | Pamplona | Navarra |
Spain | Hospital Universitario de Donostia | San Sebastián | Guipúzcoa |
Spain | Onkologikoa | San Sebastián | |
United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Oncomatryx Biopharma S.L. |
United States, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | 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 | Through study completion, an average of 24 months | |
Other | Evaluation of OMTX705 biomarkers | By measuring the changes in circulating OMTX705 biomarkers prior and after using OMTX705 as monotherapy and in combination with pembrolizumab | Through study completion, an average of 24 months. | |
Other | Evaluation of OMTX705 payload metabolites | By quantifying OMTX705 payload TAM470 metabolites prior and after using OMTX705 as monotherapy and in combination with pembrolizumab. | Through study completion, an average of 24 months. | |
Other | Evaluation of QTc prolongation | By performing electrocardiography (ECG) pre and at the end of the drug infusion. | Through study completion, an average of 24 months. | |
Other | Evaluation of cancer-associated fibroblasts (CAFs). | By measuring the changes of CAFs and inmune cells in plasma samples prior and after using OMTX705 as monotherapy and in combination with pembrolizumab. | Through study completion, an average of 24 months | |
Other | Evaluation of clinical efficacy of OMTX705 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) | Through study completion, an average of 24 months | |
Primary | Safety evaluation of OMTX705 | Frequency by grade of treatment-emergent adverse events (TEAEs). | Through study completion, an average of 24 months | |
Secondary | 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) | Through study completion, an average of 24 months | |
Secondary | Evaluation of the OMTX705 Pharmacokinetics | By assessing plasma drug concentrations of OMTX705 as monotherapy and with pembrolizumab, with Ultra-High-Performance Liquid Chromatography (UPLC-MS/MS) and immunosorbent assay (ELISA) methods | Through study completion, an average of 24 months | |
Secondary | Evaluation of OMTX705 Immunogenicity | By quantifying the formation of anti-drug antibodies (ADAs) with Meso Scale Discovery (MSD) immunoassay method. | Through study completion, an average of 24 months. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06223308 -
A Study Evaluating the Safety and Efficacy of HB0028 in Subjects With Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT05515185 -
B7-H3 Targeting CAR-T Cells Therapy for B7-H3 Positive Solid Tumors
|
Early Phase 1 | |
Completed |
NCT05508100 -
Dose Confirmation and Dose Expansion Phase 1 Study of IO-108 and IO-108 + Anti-PD-1 in Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05094804 -
A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
|
Phase 1/Phase 2 | |
Completed |
NCT02836600 -
A Study of LY3039478 in Japanese Participants With Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04890613 -
Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation
|
Phase 1 | |
Recruiting |
NCT04390737 -
Evaluate the Safety and Clinical Activity of HH2853
|
Phase 1/Phase 2 | |
Recruiting |
NCT05981703 -
A Study Investigating BGB-26808 Alone or in Combination With Tislelizumab in Participants With Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT06007482 -
A Study of ES009 in Subjects With Locally Advanced or Metastatic Solid Tumors
|
Phase 1 | |
Completed |
NCT04108676 -
Effect of Omeprazole on PK of Fluzoparib in Healthy Male Subjects
|
Phase 1 | |
Recruiting |
NCT05798611 -
Study of ART0380 in Patients With Biologically Selected Solid Tumors
|
Phase 2 | |
Recruiting |
NCT05076396 -
PM14 Administered Intravenously to Patients With Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT06008366 -
A Phase 1/2 Study of 7MW3711 in Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT06054932 -
Safety, Tolerability, and Immunogenicity of LK101 Alone in Participants With Incurable Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04825392 -
A Phase Ib Study of HX008 in Patients With Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT04242199 -
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors
|
Phase 1 | |
Not yet recruiting |
NCT06365918 -
Study of VG2025 Delivered Intraperitoneally in Patients With Advanced Solid Tumors With Carcinomatosis
|
Phase 1 | |
Recruiting |
NCT05443126 -
A Study of EP0031 in Patients With Advanced RET-altered Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05461287 -
Safety, Tolerability and Pharmacokinetics Study of QLS31904 in Patients With Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05569057 -
A Phase I Trial of SIM1811-03 in Subjects With Advanced Solid Tumors and Cutaneous T-cell Lymphoma
|
Phase 1 |