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This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VS-7375 Dose Escalation | Experimental | To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. |
|
| Cetuximab + VS-7375 Dose Escalation | Experimental | To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. |
|
| VS-7375 Recommended Phase 2 Dose Expansion | Experimental | To determine the efficacy of VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced PDAC, NSCLC, or solid tumors harboring a KRAS G12D mutation. |
|
| Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion | Experimental | To determine the efficacy of cetuximab +VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced CRC harboring a KRAS G12D mutation. |
|
| VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation | Experimental | To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab in patients with advanced 1L NSCLC harboring a KRAS G12D mutation. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VS-7375 | Drug | VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 | To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 administered on a daily oral schedule in participants with advanced solid tumors harboring a KRAS G12D mutation. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions. | Up to 2.5 years |
| Part A: To identify the MTD or MFD | To identify the MTD or MFD using a BOIN design and recommend a dose for subsequent studies of VS-7375 on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. Proportion/number of participants with DLTs during the DLT assessment period (through C1D21). | Cycle 1 (each cycle is 21 days) |
| Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen | To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen identified from Part A in participants with advanced KRAS G12D-mutated PDAC (cohort B1), NSCLC (cohort B2), and other solid tumors (cohort B3). Confirmed ORR, PFS rate, unconfirmed PR and CR rates, DCR, DOR, and PFS per RECIST v1.1. Overall Survival | Up to 2.5 years |
| Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. | To characterize the safety, tolerability, and AE profile of VS-7375 in the following combination regimens in participants with any solid tumor harboring a KRAS G12D mutation.
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions. |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: To characterize the PK of VS-7375 as 2L+ monotherapy administered on a daily oral schedule | To characterize the PK of VS-7375 as 2L+ monotherapy administered on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. Cmax derived from plasma concentrations of VS-7375. | Up to 2.5 years |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Verastem Call Center | Contact | 1 781 292 4204 | clinicaltrials@verastem.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Recruiting | Los Angeles | California | 90048 | United States |
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|
| VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion | Experimental | To determine the efficacy of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab at the RP2D in patients with advanced 1L NSCLC harboring a KRAS G12D mutation. |
|
| VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation | Experimental | To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with gemcitabine/nab-paclitaxel in patients with advanced PDAC harboring a KRAS G12D mutation. |
|
| VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion | Experimental | To determine the efficacy of VS-7375 in combination with gemcitabine/nab-paclitaxel at the RP2D in patients with advanced PDAC harboring a KRAS G12D mutation. |
|
| VS-7375 + Gemcitabine Dose Escalation | Experimental | To determine the RP2D for VS-7375 in combination with gemcitabine in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation. |
|
| VS-7375 + Gemcitabine Dose Expansion | Experimental | The determine the efficacy of VS-7375 in combination with gemcitabine at the RP2D in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation. |
|
| Cetuximab | Drug | Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). |
|
|
| Carboplatin + Pemetrexed + Pembrolizumab | Drug | A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer. |
|
| Gemcitabine | Drug | A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma. |
|
| Gemcitabine + Nab-paclitaxel | Drug | A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma. |
|
| From enrollment to the end of treatment; an average of 9 months |
| Part C: To identify a recommended dose for subsequent studies of combination dosed VS-7375. | To identify a recommended dose for subsequent studies of combination dosed VS-7375. Proportion/number of participants with DLTs during the DLT assessment period (through end of Cycle 1). | Cycle 1 (each cycle is 21 or 28 days) |
| Part D: To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C | To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C as:
Confirmed ORR, PFS rate, unconfirmed PR and CR rates, DCR, DOR, and PFS per RECIST v1.1. Overall survival | Up to 2.5 years |
| Part A: To evaluate the preliminary anticancer activity of VS-73753 as 2L+ monotherapy |
To evaluate the preliminary anticancer activity of VS-7375 as 2L+ monotherapy in participants with any KRAS G12D-mutated solid tumor. Confirmed ORR, unconfirmed PR and CR rates, DCR, and DOR per RECIST v1.1. |
| Up to 2.5 years |
| Parts B and D: To characterize the safety, tolerability, and AE profile of the recommended VS-7375 regimens from Part A and Part C | To characterize the safety, tolerability, and AE profile of the recommended VS-7375 regimens from Part A (VS-7375 monotherapy) and Part C (VS-7375 in combination with other systemic therapies), administered on a daily oral schedule in participants with KRAS G12D-mutated solid tumors. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions. | Up to 2.5 years |
| Parts B, C, and D: To continue to evaluate the PK of VS-7375 as monotherapy and in combination with other systemic therapies | To continue to evaluate the PK of VS-7375 as monotherapy and in combination with other systemic therapies in participants with KRAS G12D-mutated advanced solid tumors. Cmax derived from plasma concentrations of VS-7375. | Up to 2.5 years |
| Part C: Cohort C3: To evaluate the impact of VS-7375 on nab-paclitaxel PK | To evaluate the impact of VS-7375 on nab-paclitaxel PK in cohort C3. Change in nab-paclitaxel exposure in the presence and absence of VS-7375. | Up to 2.5 years |
| Johns Hopkins University | Recruiting | Baltimore | Maryland | 21287 | United States |
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| Massachusetts General Hospital | Recruiting | Boston | Massachusetts | 02114 | United States |
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| University of Michigan | Recruiting | Ann Arbor | Michigan | 48109 | United States |
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| Washington University School of Medicine | Recruiting | St Louis | Missouri | 63110 | United States |
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| Laura & Isaac Perlmutter Cancer Center at NYU Langone | Recruiting | New York | New York | 10016 | United States |
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| Univ of Pennsylvania, Abramson Cancer Center | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| SCRI Oncology Partners | Recruiting | Nashville | Tennessee | 37203 | United States |
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| MD Anderson Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
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| Huntsman Cancer Institute | Recruiting | Salt Lake City | Utah | 84112 | United States |
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| University of Virginia | Recruiting | Charlottesville | Virginia | 22908 | United States |
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| Virginia Cancer Specialists | Recruiting | Fairfax | Virginia | 22031 | United States |
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| Virginia Mason Medical Center | Recruiting | Seattle | Washington | 98101 | United States |
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| Peninsula and Southeast Oncology | Recruiting | Frankston | Victoria | 3199 | Australia |
|
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D015179 | Colorectal Neoplasms |
| D008175 | Lung Neoplasms |
| D009362 | Neoplasm Metastasis |
| D010190 | Pancreatic Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007414 | Intestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004701 | Endocrine Gland Neoplasms |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| D016190 | Carboplatin |
| D000068437 | Pemetrexed |
| C582435 | pembrolizumab |
| D000093542 | Gemcitabine |
| C520255 | 130-nm albumin-bound paclitaxel |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000600 | Amino Acids, Dicarboxylic |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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