Clinical trial NCT06792552: A Phase I Study of SIM0505 in Participants With Advanced Solid Tumors
Official title: A Phase I First-in-human, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0505 in Adult Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Xianxiang Medical Technology Co., Ltd.
First posted: 2025-01-24
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter phase 1 study to evaluate the safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0505 in Adult Participants with Advanced Solid Tumors


Eligibility criteria: Inclusion Criteria:

* 1. Written informed consent is obtained prior to any procedures that are not considered standard of care 2. ≥18 years of age. 3. In Part 1:

  1. Participants with histologically or cytologically confirmed advanced solid tumors, who have failed or are ineligible for standard of care therapies.
  2. Have progressed on at least one prior systematic anti-tumor regimen, and presence of at least one evaluable lesion according to RECIST Version 1.1 . For OC participants without measurable lesions, progression per GCIG CA-125 criteria is acceptable.

     4. In Part 2:

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  1. Participants with histologically or cytologically confirmed high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
  2. Have platinum-resistant disease, defined as: Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a best response of not progressive disease (PD), and then progressed between \>90 days and ≤180 days after the date of the last dose of platinum; Participants who have received ≥ 2 lines of platinum therapy must have progressed ≤180 days after the date of the last dose of platinum. Note: Time interval of progression should be calculated from the date of the last administered dose of platinum therapy to the date of progression.
  3. Have progressed on at least one prior systematic anti-tumor regimen, and presence of at least one measurable lesion according to RECIST Version 1.1 .

     5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

     6. Life expectancy of ≥12 weeks. 7. Have adequate organ function as indicated by the following laboratory values. Whole blood transfusion, blood component transfusion or colony-stimulating factors \[e.g., granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) or recombinant erythropoietin\] within 2 weeks prior to the laboratory tests are not allowed.

     8. Women of childbearing potential (WOCBP)must have a negative serum pregnancy test within 72 hours prior to the start of study treatment. WOCBP or male participants are required to use highly effective contraceptive methods , and agree to refrain from donating sperm/egg from signing of informed consent through 180 days after the last dose of study treatment.

     9. For Part 1, archival or fresh tumor tissue sample should be collected if available at screening visit. For Part 2, it is mandatory to collect archival tumor tissue sample performed within 6 months prior to consent or fresh tumor tissue sample at screening visit.

Exclusion Criteria:

1. For Part 2: has clear cell, mucinous or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer.
2. Any other malignancy within 5 years prior to the first dose of the study treatment except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence. Examples include basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.
3. Any known central nervous system (CNS) metastases.
4. History of bowel obstruction within 3 months prior to the first dose of study treatment.
5. Known psychiatric disorder or drug abuse that would interfere the study requirements.
6. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.
7. Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.
8. History of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease.
9. Prior exposure to other CDH6-targeted agents (e.g., raludotatug deruxtecan/DS-6000).
10. Has not recovered (i.e., to CTCAE version5.0 Grade 1 or to baseline) from previous anticancer therapy-induced AEs. Note: Grade ≤2 AEs with no impact on participant safety are exceptions to this criterion and may qualify for the study, e.g., Grade ≤2 hair loss and neuropathy caused by chemotherapy.
11. Is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of SIM0505. Note: This does not include participation in the follow-up phase of a study.
12. Major surgery within 2 weeks of receiving the first dose of study treatment
13. Has received prior therapies within the following time frames prior to the first dose of study treatment:

    1. Previous cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 2 weeks.
    2. Anti-cancer antibody or ADC within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study treatment.
    3. Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks.
    4. Radiation therapy \<4 weeks.
14. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.
15. Administration of below medications≤14 days prior to the first dose of SIM0505.

    1. Strong and moderate CYP3A4 inhibitors
    2. Drugs with known risk of Torsades de Pointes (TdP)
16. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
17. Active hepatitis B (HBsAg or HBcAb positive, and HBV-DNA ≥2 000 IU/mL or ≥10 000 copies/mL) or hepatitis C (HCV antibody positive and HCV RNA ≥ ULN) infection; participant with HBsAg positive or detectable HBV-DNA at screening should receive antiviral treatment as per local practice during the study.
18. Participants with clinically significant cardiovascular diseases, including but not limited to myocardial infarction, severe/unstable angina pectoris, primary cardiomyopathy, cerebrovascular accident (including transient cerebral ischemia, cerebral hemorrhage, cerebral infarction), or congestive heart failure (New York Heart Association class \>2, ) in the past 6 months prior to the first dose of the study treatment; symptomatic coronary heart disease requiring drug treatment; arrhythmia requiring drug treatment; QTcF interval \>470 msec; or uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg despite adequate drug treatment).
19. History of allogeneic organ transplantation or graft-versus-host disease.
20. Known hypersensitivity to study drug or any of the excipients.
21. Participant is pregnant or breastfeeding.
22. Other conditions that researchers consider inappropriate for inclusion.

Primary outcomes:
measure: dose escalation: Dose-limiting toxicity (DLT)
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: dose escalation: Adverse events (AEs)
timeFrame: the whole dose escalation phase，an average of 2 year
measure: dose optimization：Objective response rate (ORR)
timeFrame: the whole dose optimization phase，an average of 1.5 year
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: The first medical center of PLA general hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Changsha
country: China
facility: HunanCancer Hospital
state: Hunan
city: Jinan
country: China
facility: Cancer Hospital of Shandong First Medical University
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: