Trial Title:
A Clinical Study of JS105 in Combination With Other Anti-tumor Therapies in Patients With Solid Tumors
NCT ID:
NCT06208410
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Paclitaxel
Capecitabine
Fulvestrant
Fluzoparib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
JS105
Description:
JS105 is administered once daily, orally
Arm group label:
Arm A:JS105+Fulvestrant Injection
Arm group label:
Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets
Arm group label:
Arm C:JS105+Toripalimab Injection
Arm group label:
Arm D:JS105+Paclitaxel for Injection (Albumin Bound)
Arm group label:
Arm E:JS105+Fluzoparib Capsules
Arm group label:
Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets
Arm group label:
Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)
Intervention type:
Drug
Intervention name:
Fulvestrant injection
Description:
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 group label:
Arm A:JS105+Fulvestrant Injection
Arm group label:
Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets
Intervention type:
Drug
Intervention name:
Dalpiciclib Isetionate Tablets
Description:
Dalpiciclib Isetionate Tablets, QD, oral, taken continuously for 21 days, then stopped
for 7 days, 28 days for a cycle
Arm group label:
Arm B:JS105+Fulvestrant Injection+Dalpiciclib Isetionate Tablets
Intervention type:
Drug
Intervention name:
Toripalimab Injection
Description:
Toripalimab Injection,Intravenous infusion, once every 3 weeks, 21 days for 1 cycle
Arm group label:
Arm C:JS105+Toripalimab Injection
Arm group label:
Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)
Intervention type:
Drug
Intervention name:
Paclitaxel for Injection (Albumin Bound)
Description:
Paclitaxel for Injection (Albumin Bound),Intravenous infusion, D1, 8, 15 infusion, every
28 days for a cycle
Arm group label:
Arm D:JS105+Paclitaxel for Injection (Albumin Bound)
Arm group label:
Arm G:JS105+Toripalimab Injection+Paclitaxel for Injection (Albumin Bound)
Intervention type:
Drug
Intervention name:
Fluzoparib Capsules
Description:
Fluzoparib Capsules is administered once daily, orally
Arm group label:
Arm E:JS105+Fluzoparib Capsules
Intervention type:
Drug
Intervention name:
Pyrotinib Maleate Tablets
Description:
Pyrotinib Maleate Tablets is administered once daily, orally
Arm group label:
Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets
Intervention type:
Drug
Intervention name:
Capecitabine Tablets
Description:
Capecitabine Tablets is administered once daily, orally
Arm group label:
Arm F:JS105+Pyrotinib Maleate Tablets+Capecitabine Tablets
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Understand and voluntarily sign the informed consent form;
2. 18≤ age ≤ 75 years old, male or female;
3. 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;
4. 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;
5. 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);
- Disease progression or intolerance to standard therapy after receiving ≥1 line
of systemic therapy;
- For stage II, in the case of ovarian cancer, must be a
platinum-resistant/platinum-refractory patient (defined as disease progression
during or within 6 months of completion of platinum-containing chemotherapy)
For groups A, B, and D, stage Ib can be enrolled regardless of whether PIK3CA
is mutated or not, and stage II should have PIK3CA activating mutations, which
are determined by the central laboratory to be PIK3CA activating mutations by
the sponsor. The test results of the preferred tissue sample are used as the
basis for enrollment, and for patients who are truly unable to provide a tissue
sample that meets the requirements, a positive PIK3CA mutation of the ctDNA
test is allowed as the basis for enrollment.
6. Arm E, 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 epithelial ovarian, fallopian tube, or primary
peritoneal cancer
- Disease progression or intolerance to standard therapy after receiving ≥1 line
of systemic therapy
- For stage II, in the case of ovarian cancer, must be a
platinum-resistant/platinum-refractory patient (defined as disease progression
during or within 6 months of completion of platinum-containing chemotherapy)
7. Arm F, including the Dose Escalation Phase (Phase Ib) and Cohort Expansion Phase
(Phase II):
■ Patients with histologically or cytologically confirmed recurrent/metastatic
HER2-positive breast cancer;
■ Disease progression or intolerance to standard therapy after receiving ≥1 line of
anti-HER2 therapy;
8. Group G: including Dose Escalation Phase (Phase Ib) and Cohort Expansion Phase
(Phase II):
- Patients with histologically or cytologically confirmed triple-negative breast
cancer, i.e., HER2, ER, PR are all negative;
- Patients with first-diagnosed stage IV (AJCC 8th edition) or
recurrent/metastatic triple-negative breast cancer who are not candidates for
surgical treatment, and have not received prior systemic therapy for advanced
disease;
9. Agree to provide tumor tissue and blood samples for PIK3CA mutation testing required
for enrollment:
■Tumor tissue specimens: fresh or archival unstained sections, preferably from tumor
samples collected after the most recent disease progression or recurrence.
Formalin-fixed, paraffin-embedded (FFPE) unstained sections (at least 5 surgical
samples and 10 needle biopsy samples are recommended) are required. For patients who
are unable to provide tissue samples or the number of sections is insufficient, it
is necessary to communicate with the sponsor whether they can be enrolled;
■Freshly collected pre-treatment blood sample of at least 10ml
10. All acute toxicities due to prior antineoplastic therapy, surgery, or radiotherapy,
etc., resolved to Grade 0-1 (according to NCI CTCAE version 5.0) or the level
specified by the enrollment/exclusion criteria. Except for alopecia, pigmentation,
or other toxicities that, in the opinion of the investigator, do not pose a safety
risk to the patient and do not affect treatment compliance;
11. 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;
12. Eastern Cooperative Oncology (ECOG) performance status score: 0 or 1;
13. Expected survival ≥ 12 weeks;
14. Ability to swallow oral medications (capsules and tablets) without chewing,
breaking, crushing, opening, or otherwise altering the dosage form of the product;
15. 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
16. 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);
Exclusion Criteria:
1. 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);
2. Patients with known hypersensitivity to JS105 and/or the corresponding group of
combination drug components;
3. Received the following treatments before the first dose of the study drug:
1) 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.
4) 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:
1. History of acute pancreatitis, history of chronic pancreatitis, or presence of
pancreatic metastases within one year before screening;
2. Presence of type I diabetes mellitus or history of uncontrolled type II diabetes;
3. Ongoing active infection, unexplained fever > 38.5°C
4. Severe cardiovascular disease, including but not limited to a history of stroke or
transient ischemic attack, angina pectoris, or myocardial infarction within 6 months
before the first dose of study treatment, documented history of congestive heart
failure (New York Heart Association Class II-IV) or cardiomyopathy, uncontrolled
cardiac arrhythmia, active ventricular arrhythmia requiring medication or related
history, symptomatic coronary heart disease or unstable angina;
5. History of interstitial pneumonia, drug-induced pneumonia, radiation pneumonitis
requiring steroid treatment, or active pneumonitis with clinical symptoms, or other
moderate to severe lung diseases that seriously affect lung function;
6. Presence of gastrointestinal insufficiency or gastrointestinal disease that may
affect the swallowing (taking) or absorption of the study drug (e.g., ulcerative
disease, uncontrolled vomiting, diarrhea, malabsorption syndrome, small bowel
resection, history of active inflammatory bowel disease (such as Crohn's disease or
ulcerative colitis), etc.); 9. Known human immunodeficiency virus (HIV) positive
patient or active hepatitis B or C, except for the following:
1) Hepatitis B core antibody (HBcAb) positive and hepatitis B surface antigen (HBsAg)
negative during the screening period can participate in this study; 2) Patients who
are HBsAg positive and whose HBV DNA is less than the lower limit of detection can
be enrolled, and the risk will be assessed by the investigator, if necessary,
anti-HBV therapy should be received throughout the study treatment period to avoid
viral activation; 3) Patients with positive HCV antibody can only be enrolled if the
HCV RNA PCR test result is negative; 10. Female patients who are pregnant,
lactating, or intend to become pregnant during the study; 11. Any other clinically
significant disease or condition that, in the opinion of the investigator, could
affect protocol compliance (such as a history of psychiatric illness or substance
abuse), or affect the patient's signing of informed consent (such as drug use and
substance abuse), or would be inappropriate to participate in this clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Henan Provincial Cancer Hospital
Address:
City:
Zhengzhou
Zip:
450000
Country:
China
Status:
Recruiting
Contact:
Last name:
Jing Ding
Phone:
0371-65588251
Email:
dingjing201305@163.com
Investigator:
Last name:
Min Yan
Email:
Principal Investigator
Start date:
January 11, 2024
Completion date:
February 26, 2026
Lead sponsor:
Agency:
Risen (Suzhou) Pharma Tech Co., Ltd.
Agency class:
Industry
Source:
Risen (Suzhou) Pharma Tech Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06208410
