Clinical trial NCT06413615: A Study of FDA022-BB05 in Advanced/Metastatic Solid Tumors
Official title: A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of FDA022-BB05 in Patients with Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, Phase II study to evaluate the efficacy and safety of FDA022-BB05 for the treatment in locally advanced, unresectable, or metastatic patients with selected HER2 overexpressing/expressing solid tumors which are not eligible for curative therapy.


Eligibility criteria: Inclusion Criteria:

* Subjects fully understand and voluntarily participate in this study and sign informed consent.

Left Ventricular Ejection Fraction (LVEF) ≥ 50% within 28 days prior to first dose.

Eastern Cooperative Oncology Group performance status( PS) of 0 or 1. Life expectancy ≥ 3 months.

Histopathologically or cytologically confirmed advanced/unresectable or metastatic solid malignant tumors that is refractory to or intolerable with standard treatment, or for which no standard treatment is available:

Cohort A: Pathologically documented breast cancer that:

* Is unresectable or metastatic.
* Has a history of low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested).
* For HR-positive participants, is documented refractory to endocrine therapy, defined as having progressed on at least 1 endocrine therapy and determined by the investigator that subject would no longer benefit from further treatment from endocrine therapy.
* Was never previously HER2-positive(IHC 3+ or IHC 2+/ISH+) on prior pathology testing or was historically HER2 IHC 0 only.

Cohort B: Pathologically documented endometrial cancer that:

* Is unresectable or metastatic.
* Has a history of HER2 expression, defined as HER2 1+, 2+, or 3+ score on immunohistochemistry (IHC).
* Have had at least one prior line of platinum-based therapy (in any setting).
* Was never previously received other ADC anti-tumor treatment.

Cohort C: Metastatic or advanced solid tumor that are HER2 overexpression or mutation(Including urothelial cancer, colorectal adenocarcinoma and non-small cell lung cancer).

Exclusion Criteria:

* A treatment history of antibody-drug conjugate containing topoisomerase I inhibitors.

Subjects with one of the following conditions prior to first dose, including, but not limiting to：A major operation or severe trauma history within 4 weeks; A history of chemotherapy, targeted therapy, anti-angiogenesis therapy, biotherapy, immunotherapy, radiotherapy or other anti-tumor therapy within 4 weeks; A history of endocrine therapy within 3 weeks; A history of autologous stem cell transplant within 3 months.

Subjects with other malignant tumors in the past three years (not including cured non-melanoma skin basal cell carcinoma, cervical carcinoma in situ and other malignancies of low malignant potential that have been effectively controlled without treatment).

Subjects with symptomatic CNS metastasis (for example, cerebral edema requiring glucocorticoids therapy, or progressive CNS metastasis), not including prior cerebral and meningeal metastasis that is confirmed stable with MRI and without systematic glucocorticoids therapy.

Adverse reactions from the previous anti-tumor treatment have not yet recovered (\>Grade 2 in NCI-CTCAE 5.0, with exception of alopecia and pigmentation or other adverse reactions judged no safety risk by the investigator).

Subjects with clinically significant cardiovascular or cerebrovascular disease, including, but not limiting to:

a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.

a medical history of myocardial infarction or unstable angina within 6 months prior to screening; a QTc prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females.

Subjects with a medical history of interstitial lung disease (ILD)/pneumonia in need of glucocorticoids intervention，or with interstitial lung disease, or suspicious ILD by imaging detection at screening.

Subjects with any uncontrolled active infection within 1 week prior to first dose.

Subjects with concomitant disease potentially increasing toxicological risk. Known allergy to protein preparation or any protein drug with similar structure to FDA022-BB05.

Subjects with a History of alcohol abuse or psychotropic/narcotic drug abuse; Pregnant or lactating women. Subjects with poor compliance, or not suitable for this study as determined by the investigator due to other reasons.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 24 month
measure: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: up to 24 month
Secondary outcomes:
measure: Duration of response (DoR)
timeFrame: up to 24 month
measure: Disease control rate (DCR)
timeFrame: up to 24 month
measure: Progression free survival (PFS)
timeFrame: up to 24 month
measure: Overall survival (OS)
timeFrame: up to 24 month
measure: Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum FDA022-BB05 Following First Dose
timeFrame: From cycle1 to Cycle10 (each cycle is 21 days. )
measure: Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum FDA022-BB05 Following First Dose
timeFrame: From cycle1 to Cycle10 (each cycle is 21 days. )
measure: Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum FDA022-BB05 Following First Dose
timeFrame: From cycle1 to Cycle10 (each cycle is 21 days. )
measure: Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum FDA022-BB05 Following First Dose
timeFrame: From cycle1 to Cycle10 (each cycle is 21 days. )
measure: Number of participants who developed measurable anti-drug antibodies
timeFrame: up to 24 month
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Jian Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: