Brief Title: Study of EOC317 in Chinese Patients With Advanced Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Solid Tumor

ELIGIBILITY

Inclusion Criteria:
1. Patients is able to understand and willing to sign a written informed consent.

- 2. Patients is willing to complete the study procedure and follow-up examinations.

- 3. Male or female patients, 18 years old and above.

- 4. Dose-escalation phase: patients with histopathologically or cytopathologically confirmed advanced malignant solid tumors, including bladder cancer, cholangiocarcinoma, gastric cancer, breast cancer; dose-expansion phase: patients with histopathologically or cytopathologically confirmed advanced urothelial cancer, cholangiocarcinoma, and hepatocellular carcinoma or other advanced solid tumor with confirmed FGFR alterations.

- 5. Patients who have disease progression after previous standard of care therapy, or are unable to tolerate standard of care therapy, or have no available standard of care therapy.

- 6. Dose-escalation phase: measurable or unmeasurable lesion is acceptable; dose-expansion phase: at least one measurable lesion.
* In accordance with the response evaluation criteria in solid tumors (RECIST v1.1), measurable lesion is defined as the lesion with the longest diameter ≥10 mm and thickness scanned ≤5mm in CT or MRI. For lymph node lesion, its minor axis must be ≥15mm.

- 7. ECOG score is 0-1.

- 8. Expected survival is longer than 3 months.

- 9. No serious hematological, hepatic, or renal abnormality, in accordance with the results of the following laboratory tests:
* Hematology: neutrophil ≥1.5x10^9/L, platelet ≥75x10^9/L, hemoglobin ≥90 g/L;

- * Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ upper limit of normal x3.0; alkaline phosphatase (ALP) ≤ upper limit of normal x2.5; total bilirubin (TBIL) ≤upper limit of normal x1.5; If there is a liver tumor, hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ upper limit of normal x5.0; If there is bone metastasis or a liver tumor, alkaline phosphatase (ALP) ≤ upper limit of normal x5.0;

- * Renal function: the creatinine clearance calculated by the Cockcroft-Gault formula must be ≥ 50 mL/min.

- 10. All the adverse events is recovered to ≤ CTCAE grade 1 after previous systemic anti-tumor therapy (except alopecia and leukodermia; stable or ≤ CTCAE grade 2 neuropathy induced by previous anti-tumor therapy).

- 11. Effective contraceptive measures during the treatment and within 6 months after the last dose for male and female patients.

- 12. Dose-escalation phase: collection of tumor biopsy samples will be optional; dose-expansion phase: non-optional collection of tumor biopsy samples if the FGFR alteration is unknown during screening period;

- 13. Dose-expansion phase: liver function rating Child-Pugh grade A or grade B ( score ≥7);

- 14. Blood pressure is effectively controlled using 0 or 1 antihypertensive drugs, (blood pressure ≤150/90 mmHg), without replacing antihypertensive drugs within 1 week before day 1 of cycle 1;
Exclusion Criteria:
1. Previous use of the drug against FGFR pathway.

- 2. Having other malignant tumors other than the tumor treated in the study (exceptions: the malignant tumors cured with no recurrence within three years before enrollment in the study; completely resected basal cell and squamous cell carcinoma of skin; completely resected carcinoma in situ of any type).

- 3. Invasion of original lesion to central nervous system (CNS) with symptoms, which is unstable and requires high-dose steroid (≥10 mg Dexamethasone or equivalent dose) to control it.

- 4. Clinically significant laboratory calcium/phosphorus abnormalities in patients even after medical intervention before the first dose of study treatment, or in association with parathyroid disorder or tumor lysis syndrome.

- 5. Ophthalmic diseases known to affect visual sensitivity, e.g., retinal/corneal/lens lesions, severe glaucoma, et al.;

- 6. Active infection requiring systemic treatment (e.g., virus, bacteria, or fungus).

- 7. Receiving the following concomitant therapies prior to the start use of EOC317:
* Use of the drugs that can prolong QT interval and/or have the risk of torsades de pointes (TdP) within 7 days after the first dose, for example, quinidine, flecainide, Ibutilide;

- * Use of amiodarone within 90 days prior to the first dose.

- 8. Cardiac impairment or clinically significant cardiovascular disease, including any of the following:
* Cerebrovascular accident/stroke (within 6 months before enrollment);

- * Myocardial infarction (within 6 months before enrollment);

- * Unstable angina pectoris, congestive heart failure (New York Heart Association classification ≥grade 2) or serious arrhythmia requiring drug therapy (including prolonged QT interval/QTc>470 ms, pacemaker implantation); left ventricular ejection fraction (LVEF) <50% in echocardiography. - 9. History of active hemorrhage or gastrointestinal perforation risk in recent four weeks, or unhealed wound in recent surgery. - 10. Receiving the following therapies within the time period specified below prior to the first dose :
* Anticancer therapy ≤ 4 weeks;

- * Receiving other clinical trial drugs ≤ 4 weeks or ≤ 5 known half-lives (whichever comes later); major surgery ≤4 weeks prior to the start use of investigational product.

- 11. Long-term use of steroid, and daily use of ≥10 mg prednisone or equivalent dose (e.g., ≥0.75mg dexamethasone).

- 12. Past history of chronic diarrhea ≥ three years or presence of diarrhea prior to the EOC317 treatment.

- 13. HBsAg is positive and HBV DNA copies> normal range of detection; positive hepatitis C antibody or HCV RNA; in patients with hepatocellular carcinoma and cholangiocarcinoma, HBV tests show HBsAg-positive or HbcAb-positive, and HBV DNA ≥10^4 copies/ml or ≥2000 IU/ml (patients with undetectable HBV DNA after 2 weeks of standard antiviral therapy can be enrolled), HCV RNA >10^3 copies/ml (patients with undetectable HCV RNA after 2 weeks of standard antiviral therapy can be enrolled); HbsAg and anti-HCV are both positive at the same time;

- 14. History of human immunodeficiency virus infection, or other acquired, congenital immunodeficiency disease, or history of organ transplantation.

- 15. Known alcohol and/or drug addiction.

- 16. Previous history of neurological or psychiatric/behavioral disorder, e.g., epilepsy, history of poor compliance.

- 17. Female patients with positive results of pregnancy test or who are currently lactating

- 18. Patients who are not suitable for participation in this trial for any other reasons in investigators' judgement.

- 19. Dose-expansion phase: patients with hepatic encephalopathy; moderate or severe ascites that could not be alleviated or requiring therapeutic abdominal puncture or drainage (confirmed by B-ultrasound or CT scan within 1 week before randomization).

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Hongming Pan, M.D.

Role: Study Chair

Affiliation: Sir Run Run Shaw Hospital, Zhejiang, China

Overall Contact

Name: Echo Zhao, M.D., Jie Li, M.S.

Phone: +86-021-3175 7928, +86-021-3175 7928

Email: Echo.Zhao@eocpharma.com, jie.li@eocpharma.com

LOCATION