Clinical Trials List
Protocol NumberRMC-LUNG-101C
Not yet recruiting
2025-11-01 - 2030-09-30
Phase I
Not yet recruiting5
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase 1b/2 Open-Label, Multicenter Study of RMC-9805 with or without RMC-6236, in Combination with Other Anticancer Agents, in Patients with RAS G12D-Mutated Non-Small Cell Lung Cancer (NSCLC) – Subprotocol C
-
Sponsor
Takeda Development Center Americas, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Heng-Sheng Chao Division of Thoracic Medicine
- Hsu-ching Huang Division of Thoracic Medicine
- Yung-Hung Luo Division of Thoracic Medicine
- 廖映庭醫師 Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 林建良 Division of Hematology & Oncology
- 高婉真 Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- Shang-Wen Chen Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- 陳昭勳 Division of Hematology & Oncology
- 蕭聖諺 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- JENG-SEN TSENG Division of Thoracic Medicine
- YEN-HSIANG HUANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- 李柏昕醫師 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Jen-Yu Hung Division of Thoracic Medicine
- Hung-Ling Huang Division of Thoracic Medicine
- 李玫萱 Division of Thoracic Medicine
- 洪會洋醫師 Division of Thoracic Medicine
- 李岱晃醫師 Division of Thoracic Medicine
- 莊政皓 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Principal Investigator
Chao-Hua Chiu
Co-Principal Investigator
- 江振源醫師
- 曾羽田醫師
- Chia-Lun Chang Division of Hematology & Oncology
- 張哲華醫師
- 石智元醫師 Division of Thoracic Medicine
- 廖子堯醫師 Division of Hematology & Oncology
- 許翰琳醫師
- Shian-Jiun Lin
- Tzeon-jye Chiou Division of Hematology & Oncology
- Chih-Hsin Lee
- 楊善堯醫師 Division of Thoracic Medicine
- Kuan-Jen Bai Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
RAS G12D-Mutant Non-Small Cell Lung Cancer (NSCLC) – Subprotocol D
Objectives
To evaluate the safety and tolerability of RMC-9805
with or without RMC-6236 in combination with
pembrolizumab, with or without chemotherapy, in
patients with advanced RAS G12D-mutated solid
tumors
• To determine the RP2DS of RMC-9805 with or
without RMC-6236 in combination with
pembrolizumab, with or without chemotherapy, in
patients with advanced RAS G12D-mutated NSCLC
Test Drug
tablets
Active Ingredient
RMC-9805
RMC-6236
RMC-6236
Dosage Form
110
110
110
Dosage
300mg
20 mg、100mg
20 mg、100mg
Endpoints
• Incidence of DLTs; Part 1 and Part 2
(Cohort C3 safety lead-in only)
• Incidence of TEAEs, TRAEs, SAEs,
and clinically significant changes in
vital signs, laboratory test values, and
ECGs
(Cohort C3 safety lead-in only)
• Incidence of TEAEs, TRAEs, SAEs,
and clinically significant changes in
vital signs, laboratory test values, and
ECGs
Inclution Criteria
Patient Characteristics
1. Age: ≥ 18 years and informed consent provided.
2. Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1, with no significant decline within 2 weeks of screening. Rescreening is required if Performance Status > 1 for any reason before Day 1 of Cycle 1 (C1D1).
Disease Characteristics
3. Prior Therapy:
Part 1 Dose Exploration Group: (1) worsening or intolerance to standard therapy, or (2) deemed unsuitable or unlikely to receive significant clinical benefit from standard therapy by the trial administrator, or (3) refusal of standard therapy, or (4) no standard therapy available.
Part 1 Refill Group: For patients with locally advanced or metastatic disease, no more than 3 lines of prior systemic therapy.
- If metastatic disease develops within 6 months of treatment cessation, neoadjuvant or adjuvant therapy is considered prior therapy. - Prior targeted therapy against the mitogen-activated protein kinase (MAPK) pathway is contraindicated (e.g., direct targeted therapy against Rat Sarcoma Virus (RAS), Epidermal Growth Factor Receptor (EGFR), or v-raf murine sarcoma virus oncogene homolog B1 [BRAF]).
Part 2: No prior systemic therapy for locally advanced or metastatic disease.
- If metastatic disease develops within 6 months of stopping treatment, neoadjuvant or adjuvant therapy is considered prior therapy.
- Prior targeted therapy against the MAPK pathway is contraindicated (e.g., direct targeted therapy against RAS, EGFR, or BRAF).
4. Mutation Status: Previously confirmed RAS G12D mutations (defined as the substitution of aspartic acid for glycine at codon 12 of the KRAS, HRAS, or NRAS genes) independent of this study were determined by detecting circulating tumor deoxyribonucleotide (ctDNA) or pre-C1D1 (within a maximum of 3 years prior to C1D1) tumor tissue using deoxyribonucleotide (ctDNA) sequencing or polymerase chain reaction (PCR) in a certified laboratory according to local standards.
Patients with NSCLC harboring mutations in drivers other than RAS and for whom approved targeted therapies are available are excluded (e.g., anaplastic lymphoma kinase (ALK), reactive oxygen species-1 (ROS-1), BRAF, NSCLC with RET (rearranged during transfection) gene rearrangements, epithelial-mesenchymal transition).
5. Adequate bone marrow function: Hematological criteria must be met without the use of hematopoietic growth factors. For short-acting growth factors, hematopoietic growth factor use must be stopped for 7 days prior to laboratory testing during the screening period; for long-acting growth factors, hematopoietic growth factor use must be stopped for 14 days prior to screening (i.e., terminal elimination half-life [t½] > 48 hours [e.g., pegfilgrastim]). a. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9 /L (no growth factor support within 7 days prior to screening)
b. Heme ≥ 9.0 g/dL (no blood transfusion within 2 weeks prior to screening)
c. Platelet count ≥ 100 × 10^9 /L (no blood transfusion within 2 weeks prior to screening)
6. Adequate renal function: Estimated glomerular filtration rate ≥ 60 mL/min, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine formula or other formulas conforming to institutional guidelines, or determined using 24-hour urine collection.
7. Adequate liver function.
a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN).
b. Serum or plasma bilirubin ≤ 1.5 times ULN or < 2 times ULN (for patients with Gilbert's syndrome).
8. Adequate thyroid function: Thyroid-stimulating hormone (TSH) within the normal range, or total free triiodothyronine (T3) and thyroxine (T4) within the normal range, and no adjustment of thyroxine replacement dose within 30 days prior to C1D1.
For more details, please contact your testing physician.
1. Age: ≥ 18 years and informed consent provided.
2. Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1, with no significant decline within 2 weeks of screening. Rescreening is required if Performance Status > 1 for any reason before Day 1 of Cycle 1 (C1D1).
Disease Characteristics
3. Prior Therapy:
Part 1 Dose Exploration Group: (1) worsening or intolerance to standard therapy, or (2) deemed unsuitable or unlikely to receive significant clinical benefit from standard therapy by the trial administrator, or (3) refusal of standard therapy, or (4) no standard therapy available.
Part 1 Refill Group: For patients with locally advanced or metastatic disease, no more than 3 lines of prior systemic therapy.
- If metastatic disease develops within 6 months of treatment cessation, neoadjuvant or adjuvant therapy is considered prior therapy. - Prior targeted therapy against the mitogen-activated protein kinase (MAPK) pathway is contraindicated (e.g., direct targeted therapy against Rat Sarcoma Virus (RAS), Epidermal Growth Factor Receptor (EGFR), or v-raf murine sarcoma virus oncogene homolog B1 [BRAF]).
Part 2: No prior systemic therapy for locally advanced or metastatic disease.
- If metastatic disease develops within 6 months of stopping treatment, neoadjuvant or adjuvant therapy is considered prior therapy.
- Prior targeted therapy against the MAPK pathway is contraindicated (e.g., direct targeted therapy against RAS, EGFR, or BRAF).
4. Mutation Status: Previously confirmed RAS G12D mutations (defined as the substitution of aspartic acid for glycine at codon 12 of the KRAS, HRAS, or NRAS genes) independent of this study were determined by detecting circulating tumor deoxyribonucleotide (ctDNA) or pre-C1D1 (within a maximum of 3 years prior to C1D1) tumor tissue using deoxyribonucleotide (ctDNA) sequencing or polymerase chain reaction (PCR) in a certified laboratory according to local standards.
Patients with NSCLC harboring mutations in drivers other than RAS and for whom approved targeted therapies are available are excluded (e.g., anaplastic lymphoma kinase (ALK), reactive oxygen species-1 (ROS-1), BRAF, NSCLC with RET (rearranged during transfection) gene rearrangements, epithelial-mesenchymal transition).
5. Adequate bone marrow function: Hematological criteria must be met without the use of hematopoietic growth factors. For short-acting growth factors, hematopoietic growth factor use must be stopped for 7 days prior to laboratory testing during the screening period; for long-acting growth factors, hematopoietic growth factor use must be stopped for 14 days prior to screening (i.e., terminal elimination half-life [t½] > 48 hours [e.g., pegfilgrastim]). a. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9 /L (no growth factor support within 7 days prior to screening)
b. Heme ≥ 9.0 g/dL (no blood transfusion within 2 weeks prior to screening)
c. Platelet count ≥ 100 × 10^9 /L (no blood transfusion within 2 weeks prior to screening)
6. Adequate renal function: Estimated glomerular filtration rate ≥ 60 mL/min, calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine formula or other formulas conforming to institutional guidelines, or determined using 24-hour urine collection.
7. Adequate liver function.
a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN).
b. Serum or plasma bilirubin ≤ 1.5 times ULN or < 2 times ULN (for patients with Gilbert's syndrome).
8. Adequate thyroid function: Thyroid-stimulating hormone (TSH) within the normal range, or total free triiodothyronine (T3) and thyroxine (T4) within the normal range, and no adjustment of thyroxine replacement dose within 30 days prior to C1D1.
For more details, please contact your testing physician.
Exclusion Criteria
Disease Characteristics
1. Untreated central nervous system (CNS) metastases or meningeal disease. Patients with treated CNS metastases are eligible for inclusion if they meet all of the following criteria:
a. Radiation therapy completed ≥ 2 weeks prior to C1D1.
b. No evidence of clinical or radiographic worsening on central nervous system imaging performed within 4 weeks prior to C1D1.
c. Stable residual neurological symptoms with a Common Terminology Criteria for Adverse Events (CTCA) v5.0 grade ≤ 2, and receiving stable doses of steroids and/or antiepileptic therapy (if applicable) ≥ 2 weeks prior to C1D1.
2. Severe lung disease: A history of interstitial lung disease requiring steroid treatment, pneumonia, pulmonary fibrosis, or radiation pneumonitis within 6 months prior to C1D1, or evidence of active interstitial lung disease on screening imaging.
3. Impaired gastrointestinal (GI) function: Any condition that may affect the ability to receive or absorb the trial treatment (e.g., refractory nausea and vomiting, malabsorption, extensive bowel resection, or poorly controlled inflammatory GI diseases such as Crohn's disease or ulcerative colitis).
4. Major surgery: < 4 weeks prior to C1D1.
For more details, please contact the trial physician.
1. Untreated central nervous system (CNS) metastases or meningeal disease. Patients with treated CNS metastases are eligible for inclusion if they meet all of the following criteria:
a. Radiation therapy completed ≥ 2 weeks prior to C1D1.
b. No evidence of clinical or radiographic worsening on central nervous system imaging performed within 4 weeks prior to C1D1.
c. Stable residual neurological symptoms with a Common Terminology Criteria for Adverse Events (CTCA) v5.0 grade ≤ 2, and receiving stable doses of steroids and/or antiepileptic therapy (if applicable) ≥ 2 weeks prior to C1D1.
2. Severe lung disease: A history of interstitial lung disease requiring steroid treatment, pneumonia, pulmonary fibrosis, or radiation pneumonitis within 6 months prior to C1D1, or evidence of active interstitial lung disease on screening imaging.
3. Impaired gastrointestinal (GI) function: Any condition that may affect the ability to receive or absorb the trial treatment (e.g., refractory nausea and vomiting, malabsorption, extensive bowel resection, or poorly controlled inflammatory GI diseases such as Crohn's disease or ulcerative colitis).
4. Major surgery: < 4 weeks prior to C1D1.
For more details, please contact the trial physician.
The Estimated Number of Participants
-
Taiwan
11 participants
-
Global
126 participants
