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Also known as Arginase inhibitor, CB-1158
INCB001158 · 2 trials · 14 indications
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.
The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study treatment(s). A TEAE was defined as any adverse event that started or worsened after the first dose of study drug.
| Arm | Type | Description |
|---|---|---|
| Treatment Group A | EXPERIMENTAL | INCB001158 + FOLFOX |
| Treatment Group B | EXPERIMENTAL | INCB001158 + gemcitabine/cisplatin |
| Treatment Group C | EXPERIMENTAL | INCB001158 + paclitaxel |
| INCB00158 was administered as monotherapy at 50mg twice daily | EXPERIMENTAL | Monotherapy Part 1a: INCB001158 administered orally in patients with advanced/metastatic solid tumors. Escalating doses will be explored to determine the recommended phase 2 dose (RP2D). |
| INCB00158 was administered as monotherapy at 75mg twice daily | EXPERIMENTAL | Monotherapy Part 2a: INCB001158 administered orally at the RP2D in patients with advanced/metastatic NSCLC (EGFR and Anaplastic Lymphoma Kinase (ALK) negative) previously treated with Standard of Care (SOC). |
| INCB00158 was administered as monotherapy at 100mg twice daily | EXPERIMENTAL | Monotherapy Part 2b: INCB001158 administered orally at the RP2D in patients with advanced/metastatic CRC previously treated with SOC. |
| INCB00158 was administered as monotherapy at 150mg twice daily | EXPERIMENTAL | Monotherapy Part 2c: INCB001158 administered orally at the RP2D in patients with Bladder Cancer, Gastric or Gastroesophageal Junction (GEJ) Cancer, Renal Cell Cancer (RCC), Squamous Cell Carcinoma of the Head and Neck (SCCHN), Urothelial Cell Cancer (UCC), or Melanoma, previously treated with SOC. |
| INCB00158 was administered in combination with pembroluzimab at 50mg twice daily | EXPERIMENTAL | Monotherapy Part 2d: INCB001158 administered orally at the RP2D in patients with any tumor types in Parts 2a, 2b, or 2c. |
| INCB00158 was administered in combination with pembroluzimab at 75mg twice daily | EXPERIMENTAL | Combination Part 1b: INCB001158 and Pembrolizumab administered in patients with advanced/metastatic NSCLC, Melanoma, Urothelial Cell Cancer, MSI CRC, MSS CRC, Gastric or Gastroesophageal Junction (GEJ) Cancer, SCCHN and Mesothelioma. Multiple dose levels will be explored to determine the recommended phase 2 dose (RP2D). |
| INCB00158 was administered in combination with pembroluzimab at 100mg twice daily | EXPERIMENTAL | Part 3a: INCB001158 and Pembrolizumab the combination RP2D in patients with advanced/metastatic NSCLC (EGFR and ALK negative) with disease progression on anti-PD-1 therapy or prolonged stable disease on Pembrolizumab in the immediate prior line of therapy. |
| INCB001158 50 mg BID in combination with pembrolizumab | EXPERIMENTAL | Part C: evaluated a reduced dose of INCB001158 50 mg BID in combination with pembrolizumab with patients with moderately impaired renal function. |
| Name | Type | Description |
|---|---|---|
| INCB001158 | DRUG | Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1. |
| Oxaliplatin | DRUG | Oxaliplatin administered intravenously at the protocol-defined dose and schedule. |
| Leucovorin | DRUG | Leucovorin at the protocol-defined dose and regimen. |
| 5-Fluorouracil | DRUG | 5-Fluorouracil at the protocol-defined dose and regimen. |
| Gemcitabine | DRUG | Gemcitabine at the protocol-defined dose and regimen. |
| Cisplatin | DRUG | Cisplatin at the protocol-defined dose and regimen. |
| Paclitaxel | DRUG | Paclitaxel at the protocol-defined dose and regimen. |
| Pembrolizumab | DRUG | PD-1 Inhibitor |
Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors. * Presence of measurable disease per RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Baseline archival tumor specimen available or will...
INCB001158 is an investigational small molecule being studied for the treatment of advanced or metastatic solid tumors, including metastatic cancer and biliary tract cancer (BTC). It has been evaluated in clinical trials for conditions such as colorectal cancer, gastric cancer, head and neck cancer, lung cancer, renal cell carcinoma, bladder cancer, urothelial cancer, mesothelioma, endometrial cancer, gastroesophageal cancer, and ovarian cancer.
INCB001158 is being developed by Incyte Corporation, a biopharmaceutical company traded on the NASDAQ under the ticker symbol INCY. The company has sponsored clinical trials investigating the drug as a single agent and in combination with other therapies for advanced solid tumors.
INCB001158 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Two Phase 1 trials have been completed, evaluating the drug as a single agent and in combination with chemotherapy in patients with advanced or metastatic solid tumors.
INCB001158 has been studied in two completed clinical trials. NCT02903914 evaluated the drug as a single agent and in combination with immune checkpoint therapy in patients with advanced or metastatic solid tumors, enrolling 260 participants. NCT03314935 studied the drug in combination with chemotherapy in subjects with solid tumors, including biliary tract cancer, enrolling 149 participants.
INCB001158 is an arginase inhibitor. By inhibiting arginase, an enzyme that breaks down arginine, the drug aims to increase arginine levels in the tumor microenvironment, which may enhance anti-tumor immune responses. This mechanism is being explored as a potential treatment strategy for various solid tumors.