JYP0035 Capsules Plus Fulvestrant in PIK3CA-Mutant HR+/HER2- Advanced Breast Cancer

NCT07784036 | Not Yet Recruiting Phase 3

• 1 other identifier: JYP0035M301
• Study Type: interventional
• Target: 171
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase III Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of JYP0035 Capsules in Combination With Fulvestrant in Patients With PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Progressed on Prior Endocrine Therapy

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  Tumor imaging assessments will be performed every 8 weeks (±7 days) starting from Cycle 1 Day 1 (C1D1), and every 12 weeks (±7 days) after Week 48, until radiologic disease progression, initiation of new anti-cancer t(e.g., up to approximately 24 months)

Secondary Outcomes (3)

• Investigator-assessed PFS (RECIST v1.1)

  up to approximately 24 months

• Overall Survival (OS)

  Every 8 weeks after discontinuation of study treatment until death or loss to follow-up (e.g., up to approximately 60 months)

• Objective Response Rate (ORR) by BICR / by Investigator

  up to approximately 24 months

Study Arms (2)

JYP0035 plus Fulvestrant

EXPERIMENTAL

Drug: JYP0035 plus Fulvestrant

Placebo plus Fulvestrant

ACTIVE COMPARATOR

Drug: JYP0035 placebo plus Fulvestrant

Interventions

JYP0035 plus Fulvestrant DRUG

JYP0035 capsules 100 mg administered orally twice daily (BID). Fulvestrant 500 mg administered intramuscularly on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15), then on Day 1 of each subsequent 28-day cycle. One cycle is defined as 4 weeks (28 days).

JYP0035 plus Fulvestrant

JYP0035 placebo plus Fulvestrant DRUG

JYP0035 placebo 100 mg administered orally twice daily (BID). Fulvestrant 500 mg administered intramuscularly on Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15), then on Day 1 of each subsequent 28-day cycle. One cycle is defined as 4 weeks (28 days).

Placebo plus Fulvestrant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the clinical study and provide written informed consent (ICF).
• Aged 18 to 75 years (inclusive) at the time of signing the main ICF, of any sex.
• Histologically and/or cytologically confirmed locally advanced breast cancer (LABC) not amenable to curative surgery or metastatic breast cancer (mBC), with pathology confirming hormone receptor (HR)-positive and HER2-negative disease (based on the most recent test result); per the 2020 ASCO/CAP guidelines, HR-positive is defined as ER-positive and/or PR-positive with ≥1% of tumor cells showing positive staining, and HER2-negative is defined as IHC 0 or 1+, or IHC 2+ with negative ISH.
• Must provide a fresh or archived FFPE tumor tissue block or unstained slides for central laboratory confirmation of PIK3CA mutation status and site.
• Postmenopausal women, as well as premenopausal/perimenopausal women, are eligible; male participants and premenopausal/perimenopausal women - - must receive ovarian suppression (e.g., continuous LHRH agonist such as goserelin or leuprorelin) during the study; postmenopausal status in women is defined per NCCN Breast Cancer Guidelines 2026 V2 as age ≥60 years, or age \<60 years with amenorrhea ≥12 months and postmenopausal FSH/estradiol levels (without prior chemotherapy/endocrine therapy/suppression) or chemotherapy-induced amenorrhea ≥12 months with postmenopausal FSH/estradiol, or on tamoxifen with postmenopausal FSH/estradiol, or prior bilateral oophorectomy.
• Prior at least one line of endocrine therapy (monotherapy or combination including AI or SERM) with failure: relapse/progression during (neo)adjuvant endocrine therapy or within 12 months after adjuvant completion counted as first-line, or progression on endocrine therapy in LABC/mBC setting; in LABC/mBC, prior systemic therapy must be endocrine ≤2 lines and chemotherapy ≤1 line; note at least 80% of participants must have received prior CDK4/6 inhibitor.
• At least one measurable lesion per RECIST v1.1, or at least one osteolytic or mixed osteolytic-osteosclerotic bone lesion; sclerotic/osteoblastic-only bone lesions without measurable disease are not eligible; previously locally treated lesions may be target lesions only if documented radiologic progression occurred.
• ECOG performance status 0-1.
• Expected survival ≥6 months.
• Adequate organ function before first dose (no blood products/cytokines/EPO within 14 days, no oral leukocyte boosters within 7 days): ANC \>1.5×10⁹/L, platelets \>100×10⁹/L, hemoglobin \>90 g/L, serum creatinine \<1.5×ULN or CrCl \>50 mL/min (Cockcroft-Gault) if ≥1.5×ULN, total bilirubin \<1.5×ULN, AST/ALT \<2.5×ULN (\<5×ULN with liver mets), APTT and INR \<1.5×ULN, FPG \<7.0 mmol/L, HbA1c \<6.5%.
• Females of childbearing potential must have negative serum pregnancy test within 7 days before first dose; all fertile participants (male and female) must agree to reliable contraception (abstinence, barrier, hormonal, IUD, sterilization, etc.) during treatment and 90 days after last dose.
• Assessed by investigator as suitable for fulvestrant treatment without contraindications.

You may not qualify if:

• Presence of PTEN loss or concurrent AKT1 E17K mutation. Prior use of fulvestrant, other selective estrogen receptor degraders (SERDs), or any PI3K/AKT/mTOR inhibitor.
• Receipt of any anticancer therapy (including investigational anticancer drugs) within 4 weeks before first study drug administration, with the following exceptions:
• Nitrosoureas or mitomycin C within 6 weeks before first dose (due to delayed toxicity);
• Anticancer endocrine therapy, oral fluoropyrimidines, or small-molecule targeted drugs within 2 weeks or 5 half-lives (whichever is shorter) before first dose;
• Anticancer traditional Chinese medicine/herbal formulations within 2 weeks before first dose;
• Palliative local radiotherapy (e.g., thoracic spine or rib radiotherapy) within 2 weeks before first dose.
• Failure to recover from any prior anticancer-treatment-related adverse event or complication to baseline or ≤Grade 1, except toxicities judged by the investigator as having no safety risk (e.g., alopecia, hyperpigmentation, Grade 2 peripheral neuropathy, hypothyroidism stable on hormone replacement).
• Known active central nervous system (CNS) metastasis (note: previously treated brain metastases are allowed if radiologically stable \[no progression for ≥4 weeks on imaging performed during screening\], clinically stable, and no steroid requirement for ≥14 days before planned start; any leptomeningeal metastasis/carcinomatous meningitis is excluded).
• Major surgical procedure within 4 weeks before first dose (excluding biopsy, venous access, ureteral stent, etc.), significant trauma, or anticipated major surgery during the study; minor traumatic surgery (biopsy, endoscopy, drainage) within 7 days before first dose.
• History of another malignancy within 3 years before first dose (except cured basal cell or squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of breast, papillary thyroid carcinoma).
• Gastrointestinal disease affecting drug administration/absorption, including but not limited to bowel obstruction, dysphagia/inability to swallow tablets, refractory nausea/vomiting/diarrhea, chronic GI diseases (Crohn's disease, ulcerative colitis).
• Severe cardiovascular or cerebrovascular disease, including but not limited to:
• a) Serious cardiac rhythm or conduction abnormality requiring intervention (e.g., ventricular/supraventricular arrhythmia, II-III degree AV block, QTcF ≥470 ms in males or ≥480 ms in females \[QTcF = QT/RR\^0.33; if abnormal at screening, repeat 3 times 2-5 min apart and take mean\]); b) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other ≥Grade 3 cardio/cerebrovascular event within 6 months before first dose; c) NYHA functional class ≥II, congestive heart failure, or LVEF \<50%; d) Any factor increasing QTc prolongation or arrhythmic risk (e.g., heart failure, hypokalemia, congenital long QT syndrome, family history of long QT, known QT-prolonging concomitant drugs); e) Uncontrolled hypertension (SBP ≥160 mmHg and/or DBP ≥100 mmHg on regular antihypertensives), or history of hypertensive crisis/encephalopathy; f) Arteriovenous thrombosis, pulmonary embolism, or other severe thrombotic event within 6 months before first dose (port catheter or catheter-related thrombosis, superficial venous thrombosis not considered "severe").
• History of type 1 diabetes, type 2 diabetes, or gestational diabetes.
• History of moderate-to-severe pulmonary disease significantly affecting respiratory function or interfering with drug-related pulmonary toxicity assessment/management, including COPD, interstitial lung disease/pneumonitis, radiation pneumonitis, idiopathic pulmonary fibrosis, pulmonary embolism, severe asthma, severe obstructive/restrictive ventilatory defect, any autoimmune/connective tissue/inflammatory disease with pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's, sarcoidosis), prior pneumonectomy; active pulmonary inflammation or interstitial lung disease on screening chest imaging; active tuberculosis or active TB infection within 1 year before first dose regardless of treatment.

Sponsors & Collaborators

• Chengdu JOYO pharma Co., Ltd.: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2026
• First Posted: August 25, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: August 25, 2026

Record last verified: 2026-08