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The study is divided into two parts. The first part of the study will test various doses of ASN007 to find out the highest safe dose to test in five specific groups. The second part of the study will test how well ASN007 can control cancer.
Part A is a dose escalation study to determine a safe and tolerable dose of ASN007 for patients with advanced solid tumors. Part A will also describe how the body works on ASN007(pharmacokinetics) and the effects of ASN007 on the body (pharmacodynamics) of ASN007, through blood sampling and optional biopsies..
Part B of the study will enroll patients with particular tumor types and genetic mutations for treatment at the Recommended Phase 2 Dose. Part B will enroll patients in five groups of fifteen patients each:
Group 1: Patients with metastatic BRAF mutated melanoma Group 2: Patients with metastatic NRAS and HRAS mutated solid tumors Group 3: Patients with metastatic KRAS mutated colorectal cancer (CRC) Group 4: Patients with metastatic KRAS mutated non-small cell lung cancer (NSCLC) Group 5: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) Patients with melanoma will be required to have pre-dose and post-dose biopsies.
Group 6: Patients with metastatic MEK1, BRAF V600E, non-BRAF V600E solid tumors or BRAF fusions without prior treatment with BRAF, MEK, ERK inhibitors
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ASN007 ascending doses | Experimental | Patients will receive escalating doses of ASN007 to identify the best dose. |
|
| ASN007 RD: KRAS mutant Melanoma | Experimental | Patients with BRAF mutant metastatic melanoma will receive the recommended dose from Part A. |
|
| ASN007 RD: NRAS mutant Melanoma | Experimental | Patients with NRAS and HRAS mutant solid tumors will receive the recommended dose from Part A. |
|
| ASN007 RD: KRAS mutant metastatic CRC | Experimental | Patients with KRAS mutant CRC will receive the recommended dose from Part A |
|
| ASN007 RD: KRAS mutant NSCLC | Experimental | Patients with KRAS mutant NSCLC will receive the recommended dose from Part A |
|
| ASN007 RD: Metastatic Pancreatic Cancer |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ASN007: ascending doses | Drug | Oral drug for the treatment of advanced solid tumors |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Determine the maximum tolerated dose (MTD) of ASN007 | The MTD will be determined by evaluating the number of subjects with treatment related dose limiting toxicity. This is the primary endpoint of Part A | First 21 days |
| Part B: evaluate the overall response rate (number of Complete Responses + Partial Responses) in subjects receiving ASN007 for the treatment of metastatic melanoma, CRC, NSCLC, or pancreatic cancer. | This is the primary endpoint for Part B. | First 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Calculate the pharmacokinetic area under the plasma concentration (AUC) of ASN007 | Calculate the amount of ASN007 in the bloodstream | First 21 days |
| Calculate the maximum plasma concentration (Cmax) at steady state. |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the change from baseline in the intensity of phosphorylated ribosomal S6 kinase (RSK) found in tumor biopsies. | Evaluate the effect of ASN007 on biomarkers | Through the study, average 6 months |
| Evaluate the change from baseline in the amount of circulating tumor DNA |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Asana BioSciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center | Tampa | Florida | 33612 | United States | ||
| Massachusetts General Hospital |
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Patients with pancreatic adenocarcinoma will receive the recommended dose from Part A |
|
| ASN007 RD: MEK, All BRAF, BRAF-fusion cancers | Experimental | Patients with solid tumors will receive the recommended dose from Part A |
|
| ASN007 RD | Drug | Oral drug for the treatment of advanced solid tumors |
|
Calculate the maximum amount of ASN007 in the bloodstream
| First 21 days |
| Calculate the terminal elimination rate (T 1/2). | Calculate how fast ASN007 leaves the body | First 21 days |
Evaluate the effect of ASN007 on biomarkers |
| Every 8 weeks for the first 24 weeks, then every 12 weeks for up to 1 year |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| South Texas Accelerated Research Therapeutics | San Antonio | Texas | 78229 | United States |
| NEXT Oncology | San Antonio | Texas | 78240 | United States |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D009362 | Neoplasm Metastasis |
| D003110 | Colonic Neoplasms |
| D008545 | Melanoma |
| D008175 | Lung Neoplasms |
| D010190 | Pancreatic Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
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