A Clinical Study of JS105 in Combination With Other Anti-tumor Therapies in Patients With Solid Tumors

NCT06208410 | Recruiting Phase 1

• 1 other identifier: JS105-002-Ib/II
• Study Type: interventional
• Target: 306
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, multicenter, Phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of JS105 in combination with other anti-tumor therapies in patients with advanced solid tumors. Patients will be enrolled in two stages: a dose-escalation stage and a dose-expansion stage.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicity

  Incidence and severity of DLT events.

  At the end of Cycle 1 (each cycle is 28 days)

• MTD

  Maximum tolerated dose

  At the end of Cycle 1 (each cycle is 28 days)

• RP2D

  Recommended phase II dose

  At the end of Cycle 1 (each cycle is 28 days)

• Incidence and severity of adverse events including serious adverse events

  Abnormal changes in clinical symptoms, vital signs, physical examination, laboratory tests, electrocardiograph and other examinations.

  Up to 2 years

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Up to 2 years

• Duration of Objective Response (DOR)

  Up to 2 years

• Disease Control Rate(DCR)

  Up to 2 years

• Progression-Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Other Outcomes (1)

• The proportion of patients with PIK3CA mutations in tumor remission

  Up to 2 years

Study Arms (7)

Arm A:JS105+Fulvestrant Injection

EXPERIMENTAL

JS105 administered orally, Fulvestrant intramuscularly

Drug: JS105; Drug: Fulvestrant injection

Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets

EXPERIMENTAL

JS105 administered orally, Dalpiciclib administered orally, Fulvestrant intramuscularly

Drug: JS105; Drug: Fulvestrant injection; Drug: Dalpiciclib Isetionate Tablets

Arm C:JS105+Toripalimab Injection

EXPERIMENTAL

JS105 administered orally, Toripalimab intravenous infusion

Drug: JS105; Drug: Toripalimab Injection

Arm D:JS105+Paclitaxel for Injection (Albumin Bound)

EXPERIMENTAL

JS105 administered orally, Paclitaxel (Albumin Bound) intravenous infusion

Drug: JS105; Drug: Paclitaxel for Injection (Albumin Bound)

Arm E:JS105+Fluzoparib Capsules

EXPERIMENTAL

JS105 administered orally, Fluzoparib administered orally

Drug: JS105; Drug: Fluzoparib Capsules

Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets

EXPERIMENTAL

JS105 administered orally, Pyrotinib administered orally,Capecitabine administered orally

Drug: JS105; Drug: Pyrotinib Maleate Tablets; Drug: Capecitabine Tablets

Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)

EXPERIMENTAL

JS105 administered orally, Toripalimab intravenous infusion, Paclitaxel (Albumin Bound) intravenous infusion

Drug: JS105; Drug: Toripalimab Injection; Drug: Paclitaxel for Injection (Albumin Bound)

Interventions

JS105 DRUG

JS105 is administered once daily, orally

Arm A:JS105+Fulvestrant Injection; Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets; Arm C:JS105+Toripalimab Injection; Arm D:JS105+Paclitaxel for Injection (Albumin Bound); Arm E:JS105+Fluzoparib Capsules; Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets; Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)

Fulvestrant injection DRUG

Fulvestrant intramuscularly,The first cycle was injected once in D1 and D15, and then once in each cycle D1, and 28 days was 1 cycle

Arm A:JS105+Fulvestrant Injection; Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets

Dalpiciclib Isetionate Tablets DRUG

Dalpiciclib Isetionate Tablets, QD, oral, taken continuously for 21 days, then stopped for 7 days, 28 days for a cycle

Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets

Toripalimab Injection DRUG

Toripalimab Injection,Intravenous infusion, once every 3 weeks, 21 days for 1 cycle

Arm C:JS105+Toripalimab Injection; Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)

Paclitaxel for Injection (Albumin Bound) DRUG

Paclitaxel for Injection (Albumin Bound),Intravenous infusion, D1, 8, 15 infusion, every 28 days for a cycle

Arm D:JS105+Paclitaxel for Injection (Albumin Bound); Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)

Fluzoparib Capsules DRUG

Fluzoparib Capsules is administered once daily, orally

Arm E:JS105+Fluzoparib Capsules

Pyrotinib Maleate Tablets DRUG

Pyrotinib Maleate Tablets is administered once daily, orally

Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets

Capecitabine Tablets DRUG

Capecitabine Tablets is administered once daily, orally

Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign the informed consent form;
• ≤ age ≤ 75 years old, male or female;
• Arms A and B, including the Dose Escalation Phase (Phase Ib) and Cohort Expansion Phase (Phase II):
• Patients with histologically or cytologically confirmed recurrent/metastatic HR-positive and HER2-negative breast cancer;
• HER2 negative must meet one of the following: IHC 0, IHC 1+; IHC2+ should be further confirmed by in situ hybridization (ISH) to determine HER2 negative, and different tissue blocks can also be selected for re-testing;
• ER-positive and/or PR-positive: ER-positive requires \>10% of tumor cell nuclei in the whole section to express ER;
• For females, either postmenopausal or premenopausal/perimenopausal can be enrolled: postmenopausal, defined as meeting at least one of the following criteria: 1) age ≥ 60 years, 2) age \< 60 years, and amenorrhea ≥ 12 months, and follicle-stimulating hormone and estradiol levels in the postmenopausal range in the absence of chemotherapy, endocrine therapy, or ovarian function suppression therapy, 3) prior bilateral oophorectomy. Premenopausal or perimenopausal (i.e., does not meet postmenopausal criteria) and meets the following criteria: Started at least 2 weeks before the first dose of study drug and continuously treated with luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin or leuprolide) for the duration of study treatment
• For stage Ib, the patient has disease progression during or after prior endocrine therapy or other systemic therapy, with no limit on the number of prior lines of therapy;
• For Group A Phase II, patients meet the following criteria: disease progression or recurrence during or after prior treatment with AI with or without CDK4/6 inhibitors, ≤2 lines of systemic therapy in advanced breast cancer, ≤1 line of chemotherapy (neoadjuvant/adjuvant chemotherapy is not counted as a line of chemotherapy), and \> after completion of (neo)adjuvant endocrine therapy patients with recurrence at 12 months must receive 1 to 2 lines of systemic therapy for advanced disease to be enrolled;
• For Group B stage II, patients who meet: recurrence during or ≤ 12 months after completion of (neo)adjuvant endocrine therapy or disease progression after receiving 1st line of endocrine therapy in the advanced stage, ≤ 1st line chemotherapy in the advanced breast cancer stage are allowed;
• Arm C, including the Dose Escalation Phase (Phase Ib) and Cohort Expansion Phase (Phase II):
• Patients with histologically or cytologically confirmed recurrent/metastatic endometrial and cervical cancer;
• Disease progression or intolerance to standard therapy after receiving ≥1 line of systemic therapy;
• Group D, including the Dose Escalation Phase (Phase Ib) and Cohort Expansion Phase (Phase II):
• ■ Patients with histologically or cytologically confirmed recurrent/metastatic triple-negative breast cancer or patients with advanced gynecologic tumors (including patients with epithelial ovarian, fallopian tube or primary peritoneal cancer, endometrial cancer, and cervical cancer);

You may not qualify if:

• At least one measurable lesion (only for Phase II cohort expansion phase) or non-measurable osteolytic or mixed bone lesion (for breast cancer patients only) that meets the requirements of RECIST v1.1;
• Eastern Cooperative Oncology (ECOG) performance status score: 0 or 1;
• Expected survival ≥ 12 weeks;
• Ability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the dosage form of the product;
• Functions of vital organs, in line with the requirements:
• a. No blood transfusion blood products or hematopoietic growth factors to correct the blood cell count within 14 days before the examination creatinine clearance was calculated using the Cockcroft/Gault formula: Creatinine clearance (mL/min) = (140-age)× Body weight (kg) ×(0.85 \[females only\]) 72 × serum creatinine (mg/dl) c. For patients with FPG ≥ 100 mg/dL and/or HbA1c ≥ 5.7% (eg, prediabetes threshold) during the screening period, lifestyle changes such as dietary prescription (eg, small and frequent meals, low-carb diet, high-fiber diet, etc.) and exercise are recommended according to ADA guidelines, and endocrinologist consultation is recommended.
• d. Patients receiving anticoagulant therapy (such as low molecular weight heparin or warfarin) should be stable at the dose of anticoagulant drugs for at least 4 weeks without dose adjustment; e. Only urine routine showed urine protein ≥2+, and additional 24-hour urine protein quantification was required
• Within 7 days before the first dose of study drug, females of childbearing potential must confirm that the serum HCG test is negative and non-lactating, and female patients, as well as male patients whose partner is a female of childbearing age, need to use highly effective contraception during study treatment and within 30 days after the last dose of JS105 or during the contraceptive period specified in the label of other antineoplastic drugs, whichever occurs later, (see section 10.3 for the definition of WOCBP);
• Prior treatment with PI3K/AKT/mTOR inhibitors, prior treatment with fulvestrant and other SERDs (applicable to phase II of group A and phase II of group B);
• Patients with known hypersensitivity to JS105 and/or the corresponding group of combination drug components;
• Received the following treatments before the first dose of the study drug:
• \) Major surgery or radiotherapy within 4 weeks, or anticipated major surgery (except tumor biopsy) or radiotherapy during the study; 2) Systemic chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin; oral fluorouracil can be shortened to 2 weeks or 5 half-lives of the drug, whichever is longer), targeted therapy (small molecule targeted drugs can be shortened to 2 weeks or 5 half-lives of the drug, whichever is longer), immunotherapy or biological therapy; 3) Receiving endocrine therapy or proprietary Chinese medicine preparations with anti-tumor indications within 2 weeks.
• \) Other clinical investigational drugs (without placebo) within 4 weeks; 5) Vaccination with live attenuated vaccine within 4 weeks; 6) Received drug treatment with a known strong inhibitor or inducer of the isoenzyme CYP3A4 within 7 days (see Appendix 4 for a strong inhibitor or inducer of the isoenzyme CYP3A4); 7) Need for long-term use or use of ≥10mg/day prednisone and equivalent doses of systemic corticosteroids or immunosuppressive drugs within 2 weeks before the first dose; 4. Previous allogeneic bone marrow transplantation or solid organ transplantation; 5. Other malignancies other than study disease within 5 years before the first dose, except for malignancies that can be expected to heal after treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with radical surgery); 6. Patients with symptomatic, untreated, or ongoing central nervous system metastases requiring ongoing treatment (previously treated patients who have been stable for at least 3 months, have no disease progression as determined by imaging within 4 weeks before the first dose of the study, and all neurological symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and have stopped using radiation, surgery, or steroids at least 4 weeks before the first dose of study treatment, may be enrolled); 7. Pleural effusion, pericardial effusion, or ascites effusion (once a month or more frequent) that is uncontrolled or requires repeated drainage. Patients who need to be stable for at least 1 week before enrollment after drainage can be enrolled (stable is defined as no clear increase in pleural effusion without any intervention); 8. Concomitant and uncontrollable concomitant diseases, including but not limited to:
• History of acute pancreatitis, history of chronic pancreatitis, or presence of pancreatic metastases within one year before screening;
• Presence of type I diabetes mellitus or history of uncontrolled type II diabetes;

Sponsors & Collaborators

• Risen (Suzhou) Pharma Tech Co., Ltd.: lead

Study Sites (1)

Henan Provincial Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

MeSH Terms

Interventions

Fulvestrant; toripalimab; Paclitaxel; Injections; fluzoparib; Capecitabine

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Drug Administration Routes; Drug Therapy; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 17, 2024
• Study Start: January 11, 2024
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 26, 2027
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)