Clinical trial NCT06757335: A Phase I/II Trial to Evaluate Oral HP568 Tablets in Patients with ER+/HER2 Advanced Breast Cancer
Official title: A Multicenter, Open, Dose Escalation/dose Escalation, and Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral HP568 Tablets Alone and in Combination with Palbociclib in Patients with ER+/HER2 Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Lead sponsor: Hinova Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-03
Enrollment: 204
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and preliminary efficacy of HP568 alone and in combination with palbociclib in patients with ER+/HER2- locally advanced or metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

1. Women aged 18-75 years old (inclusive of both ends) at the time of signing the informed consent form.
2. Patients with locally advanced inoperable or recurrent or metastatic breast cancer ER+/HER2- advanced breast cancer is confirmed by histopathology have confirmed that the primary and/or metastatic lesion.
3. Previously received at least 1-line endocrine therapy (endocrine therapy duration ≥ 6 months) and ≤ 2-line chemotherapy (≤ 2-line chemotherapy limited to dose escalation stage) for the recurrence or metastasis stage of the disease. The third stage : Inclusion of patients who have not received prior treatment but are suitable for CDK4/6i therapy.
4. Disease progression confirmed by imaging occurs during or after the last systemic anti-tumor treatment before the first medication.

Exclusion Criteria:

1. Known or suspected allergy to any ingredient of HP568 formulation, and allergy to any ingredient of palbociclib (only applicable to stage III).
2. Within 42 days prior to the first administration, Fluvistran was used; Other endocrine therapies such as tamoxifen, toremifene, letrozole, anastrozole, and exemestane were used within 14 days prior to the first administration.
3. Previously received other ER-ROTAC drugs such as ARV-471.
4. Within 6 weeks before the first administration of HP568 in this study, nitrosoureas or mitomycin were used; Received any anti-tumor treatment, including immunotherapy, chemotherapy, radiotherapy, or targeted therapy, within 28 days prior to the first administration (or of the drug's 5 half lives,take the shorter one).

Primary outcomes:
measure: Stage I: the incidence of TEAE of HP568
timeFrame: From the first administration dose to 30 calendar days after the last administration dose
measure: Stage I: Incidence of dose limiting toxicity DLT, maximum tolerated dose MTD (if possible).
timeFrame: 28 days
measure: Stage III: Evaluate safety during the dose escalation phase of combination therapy
timeFrame: From the first administration dose to 30 calendar days after the last administration dose
measure: Stage III: Evaluate tolerance during the dose escalation phase of combination therapy
timeFrame: 28 days
measure: Stage III: Evaluate the 24 week clinical benefit rate (CBR) during the dose escalation phase of combination therapy
timeFrame: Until all patients have completed 24 weeks administration
measure: Stage II: 24 week clinical benefit rate (CBR)
timeFrame: Until all patients have completed 24 weeks administration
Secondary outcomes:
measure: Stage I-III: Objective response rate (ORR)
timeFrame: Until all patients have completed study（approximately 2 years）
measure: Stage I/III: 24 week clinical benefit rate (CBR)
timeFrame: Until all patients have completed 24 weeks administration
measure: Stage I-III: Disease Control Rate (DCR)
timeFrame: Until all patients have completed study（approximately 2 years）
measure: Stage I-III: Progression free survival (PFS)
timeFrame: Until all patients have completed study（approximately 2 years）
measure: Stage I-III: Duration of response(DOR)
timeFrame: Until all patients have completed study（approximately 2 years）
measure: Stage I-III: Time to Response (TTR)
timeFrame: Until all patients have completed study（approximately 2 years）
measure: Stage I-II：Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)
timeFrame: on the first day of cycle 1 and cycle 2（each cycle is 28 days）
measure: Stage I-II：Assessment of pharmacokinetic parameter maximum concentration (Cmax)
timeFrame: on the first day of cycle 1 and cycle 2（each cycle is 28 days）
measure: Stage I-II: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
timeFrame: on the first day of cycle 1 and cycle 2 (each cycle is 28 days)
measure: Stage I-II：Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)
timeFrame: on the first day of cycle 1 and cycle 2 (each cycle is 28 days)
measure: Stage III：Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)
timeFrame: on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days)
measure: Stage III: Assessment of pharmacokinetic parameter maximum concentration (Cmax)
timeFrame: on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days)
measure: Stage III: Assessment of pharmacokinetic parameter minimum concentration (Cmin)
timeFrame: on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days)
measure: Stage III: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)
timeFrame: on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days)
Other outcomes:
Locations:
Study officials:
References: