Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors.

JRCT ID: jRCT2031230712

Registered date:15/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced Solid Tumors
• Date of first enrollment: 13/06/2023
• Target sample size: 260
• Countries of recruitment: United States,Japan,Australia,Japan,France,Japan,Germany,Japan,Korea,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Part A: Dose Exploration
Participants will receive escalating doses of AMG 305.
Intervention: Drug: AMG 305

- Experimental: Part B: Dose Expansion
Participants with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer, and other solid tumors will receive the RP2D identified in Part A.
Intervention: Drug: AMG 305

Outcome(s)

Primary Outcome

1. Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 28 ]
2. Percentage of Participants who Experience Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to a maximum of 2 years ]
Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests, as assessed by the investigator, will also be reported as TEAEs.
3. Percentage of Participants who Experience Treatment-Related Adverse Events [ Time Frame: Up to a maximum of 2 years ]

Secondary Outcome

1. Maximum Serum Concentration (Cmax) of AMG 305 [ Time Frame: Up to a maximum of 2 years ]
2. Minimum Serum Concentration (Cmin) of AMG 305 [ Time Frame: Up to a maximum of 2 years ]
3. Area Under the Concentration-Time Curve (AUC) of AMG 305 [ Time Frame: Up to a maximum of 2 years ]
4. Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to a maximum of 2 years ]
ORR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), Clinical Benefit Rate (defined as BOR of CR, PR, or stable disease [SD] with duration of 24 weeks or longer) based on RECIST v1.1.
5. ORR based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST) [ Time Frame: Up to a maximum of 2 years ]
ORR is defined as immune best overall response (iBOR) of immune complete response (iCR) or immune partial response (iPR), Clinical BenefitRate (defined as iBOR of iCR, iPR, or immune stable disease [iSD] with duration of 24 weeks or longer) based on iRECIST.
6. Duration of Response (DOR) [ Time Frame: Up to a maximum of 2 years ]
DOR is defined as the time from the first documentation of objective response until the first documentation of disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST.
7. Time to Progression [ Time Frame: Up to a maximum of 2 years ]
Time to progression is defined as the time rom first AMG 305 dose until the first documentation of radiological disease progression by RECISTv1.1 and iRECIST.
8. Progression-Free Survival (PFS) [ Time Frame: Up to a maximum of 2 years ]
PFS is defined as the time from first AMG 305 dose until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST.
9. Overall Survival (OS) at 1 Year [ Time Frame: 1 year ]
10. OS at 2 Years [ Time Frame: 2 years ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Pre-screening:
1. Participant has provided informed consent prior to initiation of any pre screening study specific activities/procedures.
2. Participants with histologically or cytologically documented solid tumor diseases expressing cadherin-3 and mesothelin (by mRNA in the Cancer Genome Atlas Program [TCGA] database), including CRC, NSCLC, mesothelioma, pancreatic cancer, gastric cancer, head and neck cancer, cervical carcinoma, uterine carcinoma, and breast cancer

Clinical study:
3. Participant has provided inform consent to the main study prior to initiation of any study specific activities/procedures
4. Male or female participants age >=18 years
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
6. Participants with histologically or cytologically documented solid tumor diseases, including CRC, NSCLC, mesothelioma, pancreatic cancer, GC, head and neck cancer, cervical carcinoma, uterine carcinoma, and breast cancer. Participants must have exhausted available standard of care (SOC) systemic therapy or must not be candidates for such available therapy
7. For dose expansion cohorts: participants with at least 1 measurable lesion .10 mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study
8. Life expectancy > 3 months
9. Adequate organ function

Exclude criteria

1. Untreated central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
2. History of other malignancy within the past 2 years
3. Ongoing or active infection
4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
5. Known interstitial lung disease
6. Positive test for human immunodeficiency virus (HIV)
7. Positive hepatitis B surface antigen or positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
8. Anticancer therapies including radiotherapy (with the exception of palliative radiation) chemotherapy or molecularly targeted treatments or tyrosine kinase inhibitors (TKI) within 4 weeks or 5 half lives (whichever is longer) of administration of a first dose of study treatment; immunotherapies/monoclonal antibodies within 3 weeks of administration of a first dose of study treatment.
9. Has had a major surgery within 4 weeks of administration of a first dose of study treatment
10. Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study (eg, ulcerative colitis, Crohn's disease)
11. Live and/or live-attenuated vaccines received within 28 days (or longer, if required locally) prior to the first dose of AMG 305
12. Currently receiving treatment in another investigational device or drug study
13. Female participants of childbearing potential or male participants unwilling to use protocol specified method of contraception
14. Females who are pregnant, breastfeeding or who plan to breastfeed or become pregnant while on study
15. History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

Related Information

• Primary Sponsor: Iizumi Sakura
• Secondary ID(s): NCT05800964