Numerous Phase 1 and Phase 2 clinical trials, sponsored predominantly by the National Cancer Institute alongside pharmaceutical developers such as Hoffmann-La Roche, have evaluated the gamma-secretase inhibitor RO4929097 across a range of advanced malignancies. These studies assessed therapeutic efficacy as monotherapy or combination regimens for conditions including triple-negative breast carcinoma, pancreatic adenocarcinoma, metastatic colorectal cancer, non-small cell lung cancer, advanced prostate cancer, melanoma, and hematologic lymphomas. Although several trials achieved completed status, others evaluating combination strategies were terminated or withdrawn.
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01196416 | COMPLETED | Recurrent Melanoma; Stage IV Skin Melanoma |
National Cancer Institute (NCI) |
2010-08 | PHASE1; PHASE2 |
| NCT01122901 | TERMINATED | Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor |
National Cancer Institute (NCI) |
2010-12 | PHASE2 |
| NCT01193881 | TERMINATED | Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer |
National Cancer Institute (NCI) |
2010-08 | PHASE1 |
| NCT01154452 | COMPLETED | Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone |
National Cancer Institute (NCI) |
2010-06 | PHASE1; PHASE2 |
| NCT01131234 | COMPLETED | Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Solid Neoplasm; Male Breast Carcinoma; Recurrent Adult Brain Neoplasm; Recurrent Breast Carcinoma; Recurrent Colon Carcinoma; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Carcinoma; Recurrent Rectal Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Breast Cancer; Stage IIIC Colon Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer |
National Cancer Institute (NCI) |
2010-05 | PHASE1 |
| NCT01071564 | TERMINATED | Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma |
National Cancer Institute (NCI) |
2009-11 | PHASE1 |
| NCT01193868 | TERMINATED | Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer |
National Cancer Institute (NCI) |
2010-09 | PHASE2 |
| NCT01238133 | TERMINATED | Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma |
National Cancer Institute (NCI) |
2010-12 | PHASE1 |
| NCT01145456 | COMPLETED | Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific |
National Cancer Institute (NCI) |
2010-06 | PHASE1 |
| NCT01198184 | COMPLETED | Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific |
National Cancer Institute (NCI) |
2010-08 | PHASE1 |
| NCT01119599 | COMPLETED | Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma |
National Cancer Institute (NCI) |
2010-05 | PHASE1 |
| NCT01120275 | TERMINATED | Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma |
National Cancer Institute (NCI) |
2010-10 | PHASE2 |
| NCT01189240 | TERMINATED | Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor |
National Cancer Institute (NCI) |
2010-12 | PHASE1; PHASE2 |
| NCT01149356 | TERMINATED | Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer |
National Cancer Institute (NCI) |
2010-10 | PHASE1 |
| NCT01175343 | COMPLETED | Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer |
National Cancer Institute (NCI) |
2010-07 | PHASE2 |
| NCT01200810 | TERMINATED | Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage IV Prostate Cancer |
National Cancer Institute (NCI) |
2010-08 | PHASE2 |
| NCT01158274 | COMPLETED | Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; HER2-negative Breast Cancer; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Male Breast Cancer; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Colon Cancer; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Rectal Cancer; Stage III Small Lymphocytic Lymphoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Rectal Cancer; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia |
National Cancer Institute (NCI) |
2010-06 | PHASE1 |
| NCT01151449 | TERMINATED | Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer |
National Cancer Institute (NCI) |
2010-06 | PHASE2 |
| NCT01198535 | TERMINATED | Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer |
National Cancer Institute (NCI) |
2010-09 | PHASE1 |
| NCT01096355 | COMPLETED | Unspecified Adult Solid Tumor, Protocol Specific |
National Cancer Institute (NCI) |
2010-02 | PHASE1 |
| NCT01232829 | COMPLETED | Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer |
National Cancer Institute (NCI) |
2010-10 | PHASE2 |
| NCT01251172 | WITHDRAWN | DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma |
National Cancer Institute (NCI) |
2010-12 | PHASE2 |
| NCT01218620 | COMPLETED | Adult Solid Neoplasm |
National Cancer Institute (NCI) |
2010-09 | PHASE1 |
| NCT01141569 | COMPLETED | Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer |
National Cancer Institute (NCI) |
2010-06 | PHASE2 |
| NCT01269411 | TERMINATED | Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor |
National Cancer Institute (NCI) |
2011-07 | PHASE1 |
| NCT01192763 | TERMINATED | Adenocarcinoma of the Pancreas; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer |
National Cancer Institute (NCI) |
2010-08 | PHASE1 |
| NCT01208441 | TERMINATED | Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer |
National Cancer Institute (NCI) |
2010-11 | PHASE1 |
| NCT01217411 | TERMINATED | Adult Solid Neoplasm; Extensive Stage Lung Small Cell Carcinoma; HER2/Neu Negative; HER2/Neu Positive; Male Breast Carcinoma; Metastatic Malignant Neoplasm in the Brain; Recurrent Breast Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Recurrent Lung Small Cell Carcinoma; Recurrent Melanoma; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Lung Non-Small Cell Cancer AJCC v7 |
National Cancer Institute (NCI) |
2010-10-01 | PHASE1; PHASE2 |
| NCT01216787 | WITHDRAWN | Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma |
National Cancer Institute (NCI) |
2010-09 | PHASE2 |
| NCT01270438 | WITHDRAWN | Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer |
National Cancer Institute (NCI) |
2010-12 | PHASE2 |
| NCT01116687 | COMPLETED | Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer |
National Cancer Institute (NCI) |
2010-05 | PHASE2 |
| NCT01088763 | TERMINATED | Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific |
National Cancer Institute (NCI) |
2010-03 | PHASE1 |
| NCT01236586 | WITHDRAWN | Lymphoma; Brain Neoplasms; Sarcoma; Osteosarcoma; Wilm's Tumor |
National Cancer Institute (NCI) |
2010-10-08 | PHASE1 |
| NCT01070927 | COMPLETED | Non-Squamous Non-Small Cell Lung Cancer |
Hoffmann-La Roche |
2010-01 | PHASE2 |
(data from https://clinicaltrials.gov, updated on 2019-11-18)
Check the
RO4929097 (RG-4733)
product page for in-depth specifications, including solubility, stock solutions, MOA, and working concentrations.
Mechanism and Biochemical Profile
Appendix RUO and cGMP Quality Standards
| Quality Dimension | RUO (Research Use Only) | cGMP (Current Good Manufacturing Practice) |
|---|---|---|
| Clinical Applicability | Prohibited in human clinical trials or medical diagnostics. | Mandatory for human clinical trials (Phase I–III) and therapies. |
| Regulatory Status | Non-regulated grade; exempt from drug manufacturing laws. | Legally enforced by health authorities (e.g., FDA, EMA, NMPA). |
| Facility Environment | Unclassified analytical or research laboratories. | Validated Cleanrooms (ISO Class 5–8) with continuous monitoring. |
| Quality Control | Basic purity and activity testing. | Rigorous safety release testing (Sterility, Endotoxin, Mycoplasma). |
| Process Validation | Basic equipment calibration; no process validation required. | Full qualification (IQ/OQ/PQ) and complete batch records. |
| Quality Assurance | Vendor self-declared without required formal QMS. | Mandatory QA/QC unit, Change Control, CAPA, and vendor audits. |
| Regulatory Impact | High risk of IND rejection if used as a critical raw material. | Required for IND/NDA filings, supported by Drug Master Files (DMF). |
Footnotes
Regulatory Note: Governed by FDA (21 CFR Parts 210/211/312), EMA (EudraLex Vol 4), ICH Guidelines (E6/Q7/Q9/Q10), and compendial standards (USP <71>/<85>/<1043>).
- RO4929097 (RG-4733) Mechanism of Action: Gamma-secretase Inhibition in Tumor Cell Research
- RO4929097 (RG-4733): Selectivity & Specificity
- RO4929097 (RG-4733) Working Concentration | Cell Culture | Treatment
- RO4929097 (RG-4733) Solubility in DMSO
- RO4929097 (RG-4733) Stock Solution
- RO4929097 (RG-4733) Storage
- RO4929097 (RG-4733) Stability
- RO4929097 (RG-4733) Combination Database
- RO4929097 (RG-4733) Molecular Weight
- RO4929097 (RG-4733) SMILES
- RO4929097 (RG-4733) CAS Number
- RO4929097 (RG-4733) Chemical Structure (2D and 3D)
- RO4929097 (RG-4733) IC50 for Cell-based and Cell-free Assays
- RO4929097 (RG-4733) APExBIO (A4005)? Try a better option.
- RO4929097 (RG-4733) Cayman (19996)? Try a better option.
- RO4929097 (RG-4733) MedChemExpress (HY-11102)? Try a better option.
- RO4929097 (RG-4733) Sigma (SML4098)? Try a better option.
- RO4929097 (RG-4733) SDS｜MSDS
Note: Technical data last updated: Sep 1, 2026.