Clinical Trials List
Protocol NumberDCC-3116-01-001
NCT Number(ClinicalTrials.gov Identfier)NCT04892017
Completed
2025-09-01 - 2028-09-01
Phase I/II
Recruiting4
ICD-10C69.40
Malignant neoplasm of unspecified ciliary body
ICD-10C69.41
Malignant neoplasm of right ciliary body
ICD-10C69.42
Malignant neoplasm of left ciliary body
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9190.0
Malignant neoplasm of eyeball, except conjunctiva, cornea, retina and choroid
A Phase 1/2, First in Human Study of DCC 3116 as Monotherapy and in Combination with RAS/MAPK Pathway Inhibitors in Patients with Advanced or Metastatic Solid Tumors with RAS/MAPK Pathway Mutations
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
IQVIA RDS Taiwan Ltd.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/10/14
Investigators and Locations
Co-Principal Investigator
- Jih-Hsiang Lee 無
- 徐偉勛 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Wen-Chi Chou
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced or Metastatic Solid Tumors With RAS/MAPK Pathway Mutations
Objectives
Primary Objectives:
Dose Extension Phase (Part 2):
• Evaluate the objective response rate (ORR) of the concomitant therapy in each extended cohort under RP2D using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Secondary Objectives:
Dose Extension Phase (Part 2):
• Further describe the efficacy characteristics of DCC 3116 as monotherapy, in combination with trametinib, in combination with binimetinib, and in combination with sotorasib in the extended cohorts under RP2D.
• Further describe the pharmacokinetic (PK) characteristics of DCC 3116 in combination with trametinib.
• Further describe the pharmacokinetic (PK) characteristics of DCC 3116 in combination with binimetinib.
• Further describe the pharmacokinetic (PK) characteristics of DCC 3116 in combination with sotorasib.
• Evaluate the safety and tolerability of DCC 3116 in combination with trametinib.
• Evaluate DCC 3116 in combination with trametinib. Safety and tolerability of DCC 3116 with binimetinib
• Evaluation of the safety and tolerability of DCC 3116 with sotorasib
Test Drug
DCC-3116
Active Ingredient
DCC-3116
Dosage Form
Tablet delayed release
Dosage
25 and 100 mg
Endpoints
Dose Extension Phase (Part 2): Efficacy: The primary efficacy endpoint for the dose extension phase (Part 2) will be ORR, based on the trial administrator's assessment, defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1.
Inclution Criteria
Participants must meet all of the following criteria to be eligible for this trial:
1. Male or female participants aged ≥18 years
2. Dose escalation period (Part 1):
a. Pathologically confirmed diagnosis of advanced or metastatic solid tumors with a history of RAS, NF1, or RAF mutations. A molecular pathology report documenting the RAS, NF1, or RAF mutation status must be available.
b. Progression despite standard therapy, or failure to tolerate or failure to respond to standard therapy as determined by the trial administrator. Participants must have received at least one line of prior anticancer therapy and have a life expectancy of more than 3 months.
i. Participants with a BRAF V600E or V600K mutation record must have received approved treatment known to provide clinical benefit prior to enrollment in the trial.
ii. Participants enrolled in the DCC 3116 and sotorasib cohort (Group D) must have a KRAS G12C mutation and may have received or may not have received prior treatment with a G12C inhibitor.
3. Dose Extension Phase (Part 2): Disease progression despite the following standard treatments, or, in the opinion of the trial administrator, ineffectiveness or intolerance to standard treatment.
a. NSCLC participants with a KRAS G12C mutation
i. Must be pathologically confirmed NSCLC and have a documented KRAS G12C mutation. 1. Must have a molecular pathology report documenting KRAS G12C mutation status.
ii. Must have received at least one line of systemic therapy for advanced or metastatic cancer and, according to the trial administrator, have a life expectancy of more than 3 months.
iii. Must not have previously received sotorasib or other KRAS G12C inhibitor therapy.
4. If collection is possible during the screening period and the trial administrator deems the risk acceptable, a fresh tumor slide from the primary or metastatic cancer lesion must be provided.
5. Must have at least one lesion measurable according to the Responsive Criteria in Solid Tumor Response (RECIST) version 1.1.
6. Performance status at the time of screening, Eastern Cooperative Oncology Group (ECOG):
• Dose escalation phase: 0 to 2
• Dose extension phase: 0 to 1
7. Screening by the following laboratories (local laboratory for the dose escalation phase [Part 1], dose extension phase [Part 2]). The central laboratory assessment showed adequate organ function and bone marrow reserves:
a. Bone marrow function: Absolute neutrophil count (ANC) ≥1,500/μL; heme ≥8 g/dL and no erythrocyte thickening fluid transfusion received within the past 14 days; platelet count ≥75,000/μL
b. Liver function: For participants without liver metastases, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or for participants with liver metastases, serum AST ≤5 × ULN and ALT ≤5 × ULN; serum total bilirubin ≤1.5 × ULN, except for participants known to have Gilbert's syndrome, who are eligible to participate without binimetinib. c. Renal function: Creatinine clearance ≥50 mL/min/1.73 m2, estimated according to the Chronic Kidney Disease Epidemiological Collaborative Program formula.
d. Coagulation function: Prothrombin time (PT), International normalized ratio (INR), Partial thromboplastin time (PTT), or activated PTT (aPTT) ≤1.5×ULN.
Note: Participants who have received stable anticoagulant maintenance therapy for at least 30 days before using the investigational drug must have a PT/INR measurement result >1.5×ULN, provided that the trial administrator determines that the participant is suitable for the trial and assesses that the risk is within an acceptable range, and they may be included in the screening and cycle 2, period 1. The treatment was interrupted due to tumor biopsy collection. Sufficient justification must be provided to the trial client before enrollment.
e. Corrected serum calcium >8.0 mg/dL, serum sodium >130 mmol/L
8. Must be able to take the medication orally
9. Female participants of childbearing potential must:
a. Have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at screening, a negative pregnancy test before taking the first dose of the trial drug on day 1 of cycle 1, and
b. Consent to use two methods of contraception, one of which must be highly effective, throughout the trial, and for at least 120 days after the last dose of DCC-3116 monotherapy, in combination with trametinib, in combination with binimetinib, or in combination with sotorasib.
10. Male participants must:
a. Agree to use two contraceptive methods, one of which must be highly effective, throughout the trial and for 120 days after the last dose of DCC-3116 monotherapy, in combination with trametinib, in combination with binimetinib, or in combination with sotorasib.
b. Avoid sperm donation before the first dose of the investigational drug and for 120 days after the last dose of DCC-3116 monotherapy, in combination with trametinib, in combination with binimetinib, or in combination with sotorasib.
11. Participants must understand and adhere to the trial protocol and must sign a participant consent form; a signed informed consent form (ICF) must be obtained before any trial-specific procedure.
1. Male or female participants aged ≥18 years
2. Dose escalation period (Part 1):
a. Pathologically confirmed diagnosis of advanced or metastatic solid tumors with a history of RAS, NF1, or RAF mutations. A molecular pathology report documenting the RAS, NF1, or RAF mutation status must be available.
b. Progression despite standard therapy, or failure to tolerate or failure to respond to standard therapy as determined by the trial administrator. Participants must have received at least one line of prior anticancer therapy and have a life expectancy of more than 3 months.
i. Participants with a BRAF V600E or V600K mutation record must have received approved treatment known to provide clinical benefit prior to enrollment in the trial.
ii. Participants enrolled in the DCC 3116 and sotorasib cohort (Group D) must have a KRAS G12C mutation and may have received or may not have received prior treatment with a G12C inhibitor.
3. Dose Extension Phase (Part 2): Disease progression despite the following standard treatments, or, in the opinion of the trial administrator, ineffectiveness or intolerance to standard treatment.
a. NSCLC participants with a KRAS G12C mutation
i. Must be pathologically confirmed NSCLC and have a documented KRAS G12C mutation. 1. Must have a molecular pathology report documenting KRAS G12C mutation status.
ii. Must have received at least one line of systemic therapy for advanced or metastatic cancer and, according to the trial administrator, have a life expectancy of more than 3 months.
iii. Must not have previously received sotorasib or other KRAS G12C inhibitor therapy.
4. If collection is possible during the screening period and the trial administrator deems the risk acceptable, a fresh tumor slide from the primary or metastatic cancer lesion must be provided.
5. Must have at least one lesion measurable according to the Responsive Criteria in Solid Tumor Response (RECIST) version 1.1.
6. Performance status at the time of screening, Eastern Cooperative Oncology Group (ECOG):
• Dose escalation phase: 0 to 2
• Dose extension phase: 0 to 1
7. Screening by the following laboratories (local laboratory for the dose escalation phase [Part 1], dose extension phase [Part 2]). The central laboratory assessment showed adequate organ function and bone marrow reserves:
a. Bone marrow function: Absolute neutrophil count (ANC) ≥1,500/μL; heme ≥8 g/dL and no erythrocyte thickening fluid transfusion received within the past 14 days; platelet count ≥75,000/μL
b. Liver function: For participants without liver metastases, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or for participants with liver metastases, serum AST ≤5 × ULN and ALT ≤5 × ULN; serum total bilirubin ≤1.5 × ULN, except for participants known to have Gilbert's syndrome, who are eligible to participate without binimetinib. c. Renal function: Creatinine clearance ≥50 mL/min/1.73 m2, estimated according to the Chronic Kidney Disease Epidemiological Collaborative Program formula.
d. Coagulation function: Prothrombin time (PT), International normalized ratio (INR), Partial thromboplastin time (PTT), or activated PTT (aPTT) ≤1.5×ULN.
Note: Participants who have received stable anticoagulant maintenance therapy for at least 30 days before using the investigational drug must have a PT/INR measurement result >1.5×ULN, provided that the trial administrator determines that the participant is suitable for the trial and assesses that the risk is within an acceptable range, and they may be included in the screening and cycle 2, period 1. The treatment was interrupted due to tumor biopsy collection. Sufficient justification must be provided to the trial client before enrollment.
e. Corrected serum calcium >8.0 mg/dL, serum sodium >130 mmol/L
8. Must be able to take the medication orally
9. Female participants of childbearing potential must:
a. Have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at screening, a negative pregnancy test before taking the first dose of the trial drug on day 1 of cycle 1, and
b. Consent to use two methods of contraception, one of which must be highly effective, throughout the trial, and for at least 120 days after the last dose of DCC-3116 monotherapy, in combination with trametinib, in combination with binimetinib, or in combination with sotorasib.
10. Male participants must:
a. Agree to use two contraceptive methods, one of which must be highly effective, throughout the trial and for 120 days after the last dose of DCC-3116 monotherapy, in combination with trametinib, in combination with binimetinib, or in combination with sotorasib.
b. Avoid sperm donation before the first dose of the investigational drug and for 120 days after the last dose of DCC-3116 monotherapy, in combination with trametinib, in combination with binimetinib, or in combination with sotorasib.
11. Participants must understand and adhere to the trial protocol and must sign a participant consent form; a signed informed consent form (ICF) must be obtained before any trial-specific procedure.
Exclusion Criteria
Participants meeting any of the following criteria will be excluded from this trial:
1. Participants must not have received the following medications during the specified period prior to their first dose of the investigational drug:
a. Prior treatment with a known potent or moderate CYP3A4 or P-glycoprotein (P-gp) inhibitor or inducer (for anticancer or other reasons) (see Section 9.8.3), including certain herbal remedies (e.g., St. John's wort): 14 days or 5 times the drug's half-life (whichever is longer).
b. Prior treatment with other anticancer therapies, or any investigational therapy used for the participant's condition with a known safety and pharmacokinetic (PK) record: 14 days or 5 times the drug's half-life (whichever is shorter).
c. Investigational therapy with an unknown safety and PK record: 28 days. If sufficient data from the investigational treatment indicate that the risk of drug-drug interactions and late toxicities from prior treatment are low, the trial commissioner's medical monitor may allow a shorter washout period (14 days).
d. Grapefruit or grapefruit juice: 14 days
2. A prior or concurrent history of a malignant tumor requiring treatment, or an active cancer expected to require treatment during this trial. Hormone maintenance therapy is permitted after curative treatment for breast or prostate cancer, provided the medication used is not a prohibited drug. Participants with a history of malignant tumors who have received curative treatment and have undergone at least one follow-up assessment without evidence of disease may be considered.
3. Prior to receiving the first dose of the investigational drug, all toxicities of prior treatment have not resolved to ≤Grade 1 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI CTCAE version 5.0) or returned to the participant's baseline status (excluding hair loss). Participant baseline status is defined as no change in severity within 28 days prior to signing the participant consent form.
4. Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, except in the following cases:
• If there is a history of brain metastases, they must remain stable for at least 6 months (no new metastatic lesions seen at screening compared to previous scans, and no evidence of known metastatic lesions worsening).
• If there is a history of leptomeningeal disease, it must have cleared for at least 6 months prior to screening.
• If neurological symptoms consistent with CNS disease are present, no new such symptoms or exacerbations should have occurred within at least 6 months prior to screening.
• If there is a history of CNS metastases or leptomeningeal disease, further treatment is no longer necessary.
5. Within 6 months prior to receiving the first dose of the investigational drug, the patient has New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled heart disease, such as angina, clinically significant arrhythmia requiring treatment, uncontrolled hypertension, congestive heart failure, or myocardial infarction.
6. At screening, the patient has a QT interval prolongation (QTcF) corrected according to the Fridericia formula (QTcF) with multiple findings of QTcF > 450 ms (male) or > 470 ms (female), or a history of long QT syndrome in Part 1. Three repeated 12-lead electrocardiograms (ECGs) confirmed a mean QTcF > 450 ms (male) or > 470 ms (female) at screening, or a history of long QT syndrome in Part 2.
7. Left ventricular ejection fraction (LVEF) <50% at screening.
8. A systemic arterial thrombotic or embolic event, such as a cerebrovascular accident (including ischemic attack) or moderate hemoptysis, occurred within 6 months prior to receiving the first dose of the investigational drug.
9. A systemic venous thrombotic event (e.g., deep vein thrombosis) or pulmonary event (e.g., pulmonary embolism) occurred within 1 month prior to starting the investigational drug.
Note: Participants who experienced a thromboembolic event before receiving the first dose of the investigational drug and are currently receiving stable anticoagulation therapy, or who do not require anticoagulation therapy, are eligible.
10. Suffering from malabsorption syndrome, or other conditions deemed by the trial administrator to be sufficient to affect oral absorption.
11. Underwent major surgery within 4 weeks prior to receiving the first dose of the investigational drug. All surgical wounds must be healed and free from infection or dehiscence before receiving the first dose of the investigational drug.
12. Any other significant clinical complication, such as uncontrolled lung disease, active infection, or any other condition deemed by the trial administrator to potentially affect adherence to the trial protocol, interfere with the interpretation of trial results, or expose the participant to safety risks.
13. Known allergic or hypersensitivity reactions to any component of DCC-3116, trametinib, binimetinib, sotorasib, or any of its excipients. Please refer to the current version of IB for a list of excipients used in DCC 3116. For information on the excipients of trametinib, binimetinib, and sotorasib, please refer to the drug leaflet.
14. For participants receiving DCC-3116 in combination with trametinib or DCC-3116 in combination with binimetinib: Those who discontinued treatment with trametinib or binimetinib due to unacceptable adverse events (AEs) identified as being related to trametinib or binimetinib. An exception is given to participants who must discontinue previous trametinib treatment due to fever; these participants may be considered for inclusion in the DCC-3116 in combination with binimetinib group.
15. For participants receiving DCC-3116 in combination with sotorasib in Part 1 of dose escalation: those who discontinued treatment with sotorasib due to poor tolerability caused by a previously identified sotorasib-related adverse event (AE).
16. For participants receiving DCC-3116 in combination with sotorasib: those using proton pump inhibitors (PPIs) and H2 receptor antagonists who were unable to discontinue treatment 3 days prior to the start of investigational drug administration.
17. Known HIV infection is an exclusion criterion, except for those meeting all of the following criteria:
• CD4 count > 350/μL
• No opportunistic infection definitively classified as AIDS within the past 12 months
• Continuous use of a stable antiretroviral drug not prohibited by the trial program (Section 9.8.3) for at least 4 weeks prior to enrollment, and an HIV viral load below 400 copies/mL 18. Known hepatitis B virus (HBV) infection is an exclusion criterion unless the HBV DNA viral load test is negative and the participant has been on a course of HBV suppression therapy not prohibited by the trial program for at least 4 weeks prior to enrollment.
19. Known hepatitis C virus (HCV) infection is an exclusion criterion unless the HCV RNA viral load test is negative and the participant has completed curative HCV treatment or has been on a course of HCV therapy not prohibited by the trial program for at least 4 weeks prior to enrollment.
20. Female participants who are pregnant or breastfeeding.
21. Participants currently enrolled in an invasive trial. This is acceptable if the participant is enrolled in a non-invasive trial (including observational trials).
22. For participants receiving DCC-3116 and binimetinib in combination: Known Gilbert's syndrome.
1. Participants must not have received the following medications during the specified period prior to their first dose of the investigational drug:
a. Prior treatment with a known potent or moderate CYP3A4 or P-glycoprotein (P-gp) inhibitor or inducer (for anticancer or other reasons) (see Section 9.8.3), including certain herbal remedies (e.g., St. John's wort): 14 days or 5 times the drug's half-life (whichever is longer).
b. Prior treatment with other anticancer therapies, or any investigational therapy used for the participant's condition with a known safety and pharmacokinetic (PK) record: 14 days or 5 times the drug's half-life (whichever is shorter).
c. Investigational therapy with an unknown safety and PK record: 28 days. If sufficient data from the investigational treatment indicate that the risk of drug-drug interactions and late toxicities from prior treatment are low, the trial commissioner's medical monitor may allow a shorter washout period (14 days).
d. Grapefruit or grapefruit juice: 14 days
2. A prior or concurrent history of a malignant tumor requiring treatment, or an active cancer expected to require treatment during this trial. Hormone maintenance therapy is permitted after curative treatment for breast or prostate cancer, provided the medication used is not a prohibited drug. Participants with a history of malignant tumors who have received curative treatment and have undergone at least one follow-up assessment without evidence of disease may be considered.
3. Prior to receiving the first dose of the investigational drug, all toxicities of prior treatment have not resolved to ≤Grade 1 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI CTCAE version 5.0) or returned to the participant's baseline status (excluding hair loss). Participant baseline status is defined as no change in severity within 28 days prior to signing the participant consent form.
4. Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, except in the following cases:
• If there is a history of brain metastases, they must remain stable for at least 6 months (no new metastatic lesions seen at screening compared to previous scans, and no evidence of known metastatic lesions worsening).
• If there is a history of leptomeningeal disease, it must have cleared for at least 6 months prior to screening.
• If neurological symptoms consistent with CNS disease are present, no new such symptoms or exacerbations should have occurred within at least 6 months prior to screening.
• If there is a history of CNS metastases or leptomeningeal disease, further treatment is no longer necessary.
5. Within 6 months prior to receiving the first dose of the investigational drug, the patient has New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled heart disease, such as angina, clinically significant arrhythmia requiring treatment, uncontrolled hypertension, congestive heart failure, or myocardial infarction.
6. At screening, the patient has a QT interval prolongation (QTcF) corrected according to the Fridericia formula (QTcF) with multiple findings of QTcF > 450 ms (male) or > 470 ms (female), or a history of long QT syndrome in Part 1. Three repeated 12-lead electrocardiograms (ECGs) confirmed a mean QTcF > 450 ms (male) or > 470 ms (female) at screening, or a history of long QT syndrome in Part 2.
7. Left ventricular ejection fraction (LVEF) <50% at screening.
8. A systemic arterial thrombotic or embolic event, such as a cerebrovascular accident (including ischemic attack) or moderate hemoptysis, occurred within 6 months prior to receiving the first dose of the investigational drug.
9. A systemic venous thrombotic event (e.g., deep vein thrombosis) or pulmonary event (e.g., pulmonary embolism) occurred within 1 month prior to starting the investigational drug.
Note: Participants who experienced a thromboembolic event before receiving the first dose of the investigational drug and are currently receiving stable anticoagulation therapy, or who do not require anticoagulation therapy, are eligible.
10. Suffering from malabsorption syndrome, or other conditions deemed by the trial administrator to be sufficient to affect oral absorption.
11. Underwent major surgery within 4 weeks prior to receiving the first dose of the investigational drug. All surgical wounds must be healed and free from infection or dehiscence before receiving the first dose of the investigational drug.
12. Any other significant clinical complication, such as uncontrolled lung disease, active infection, or any other condition deemed by the trial administrator to potentially affect adherence to the trial protocol, interfere with the interpretation of trial results, or expose the participant to safety risks.
13. Known allergic or hypersensitivity reactions to any component of DCC-3116, trametinib, binimetinib, sotorasib, or any of its excipients. Please refer to the current version of IB for a list of excipients used in DCC 3116. For information on the excipients of trametinib, binimetinib, and sotorasib, please refer to the drug leaflet.
14. For participants receiving DCC-3116 in combination with trametinib or DCC-3116 in combination with binimetinib: Those who discontinued treatment with trametinib or binimetinib due to unacceptable adverse events (AEs) identified as being related to trametinib or binimetinib. An exception is given to participants who must discontinue previous trametinib treatment due to fever; these participants may be considered for inclusion in the DCC-3116 in combination with binimetinib group.
15. For participants receiving DCC-3116 in combination with sotorasib in Part 1 of dose escalation: those who discontinued treatment with sotorasib due to poor tolerability caused by a previously identified sotorasib-related adverse event (AE).
16. For participants receiving DCC-3116 in combination with sotorasib: those using proton pump inhibitors (PPIs) and H2 receptor antagonists who were unable to discontinue treatment 3 days prior to the start of investigational drug administration.
17. Known HIV infection is an exclusion criterion, except for those meeting all of the following criteria:
• CD4 count > 350/μL
• No opportunistic infection definitively classified as AIDS within the past 12 months
• Continuous use of a stable antiretroviral drug not prohibited by the trial program (Section 9.8.3) for at least 4 weeks prior to enrollment, and an HIV viral load below 400 copies/mL 18. Known hepatitis B virus (HBV) infection is an exclusion criterion unless the HBV DNA viral load test is negative and the participant has been on a course of HBV suppression therapy not prohibited by the trial program for at least 4 weeks prior to enrollment.
19. Known hepatitis C virus (HCV) infection is an exclusion criterion unless the HCV RNA viral load test is negative and the participant has completed curative HCV treatment or has been on a course of HCV therapy not prohibited by the trial program for at least 4 weeks prior to enrollment.
20. Female participants who are pregnant or breastfeeding.
21. Participants currently enrolled in an invasive trial. This is acceptable if the participant is enrolled in a non-invasive trial (including observational trials).
22. For participants receiving DCC-3116 and binimetinib in combination: Known Gilbert's syndrome.
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
88 participants
