Advanced Malignant Solid TumorPhase 1NCT06592417
To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors
A Phase 1 study testing JSKN016 injection in people with Advanced Malignant Solid Tumor, run by Jiangsu Alphamab Biopharmaceuticals Co., Ltd at 2 sites in China.
Trial summary
This is a Phase I open, multi-center, first-in-human study evaluating JSKN016 in subjects with advanced metastatic solid tumors, divided into dose escalation and dose extension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Tumor
- What is being tested?
- JSKN016 injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 2 sitesChina
- Study dates
- 30 Apr 2024to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. The subjects were ≥18 years old on the day of signing the informed consent, male or female; 3. Subjects with histologically and/or cytologically confirmed advanced unresectable or metastatic epithelial malignancies that have failed or are intolerable to previous standard therapies, preferentially but not limited to the following types: AGA-positive non-small cell lung cancer, HER2 IHC 0 breast cancer, etc.
- 4. For AGA-positive NSCLC, the presence of at least one of the following mutations is required; EGFR, ALK, ROS1, NTRK, BRAF V600, MET exon 14, RET, KRAS G12C, or HER2;
- For the enrolled subjects, the above driver gene mutations were not tested, but the previous test results confirmed by the investigators were accepted;
- If only EGFR overexpression without driver gene mutation can not be included;
- Prior osimertinib therapy is required if EGFR T790M mutation is present;
- Participants had to have failed at least one prior targeted therapy and at least platinum-based chemotherapy with or without an immune checkpoint inhibitor or antiangiogenic agent; 5. Breast cancer patients with HER2 IHC 0 expression, regardless of hormone receptor (HR) expression, could be enrolled according to the results of IHC examination in our center.
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- 6. At least one measurable lesion at baseline according to RECIST 1.1 criteria. Measurable disease required either no previous local treatment (e.g., radiotherapy) or evidence of disease progression after local treatment.
- 7. Expected survival time ≥3 months; 8. ECOG score 0 or 1; 9. Female subjects of childbearing potential or male subjects with a fertile partner agreed to use highly effective contraception from the time they provided written informed consent until 24 weeks after the last dose. Female subjects of childbearing potential had to have a negative serum/urine pregnancy test within 7 days before randomization (for women of childbearing age, see Appendix 2).
- 10. Adequate organ function within 7 days before randomization:
- Bone marrow function: absolute neutrophil count ≥1.5×109/L; Hemoglobin ≥90 g/L; Platelet count ≥100×109/L (no whole blood or blood component transfusion within 14 days before randomization; No administration of hematopoietic cytokines within 7 days before randomization).
- Liver function (based on the normal value of each clinical research center) : total bilirubin < 1.5 times the upper limit of normal value (ULN, total bilirubin in subjects with liver metastasis ≤3 x ULN); ALT/AST≤3×ULN (≤5×ULN in patients with liver metastasis); Albumin ≥28g/L; Renal function: serum creatinine ≤1.5 times the upper limit of normal, or creatinine clearance (Ccr) calculated according to Cockcroft-Gault formula (see Appendix 4) ≥ 60 mL/min; Coagulation function: INR or PT≤ 1.5x ULN, and aPTT≤ 1.5x ULN (low stable dose of anticoagulant, such as aspirin 100 mg/ day is allowed); 11. Left ventricular ejection fraction (LVEF) ≥50% (by echocardiography [ECHO]); 12. Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.
Who cannot join
- 1. Patients with symptoms of active central nervous system metastases, except those with stable parenchymal brain metastases as assessed by investigators, were defined as seizure-free for more than 12 weeks with or without the use of antiepileptic drugs; No need for glucocorticoids; At least one MRI showed that the patient was stable on imaging. Or stable after treatment for more than 1 month without symptoms; 2. Received any investigational drug within 28 days before dosing; 3. Receipt of other antineoplastic therapy within 28 days before dose or within 5 half-lives of previous antineoplastic drugs, whichever is shorter but requires a minimum of 14 days; Received Chinese herbal medicine with clear anti-tumor indications within 14 days before drug administration; 4. Local palliative treatment within 14 days before administration; 5. Major surgical treatment (such as transabdominal or transthoracic surgery) within 28 days before drug administration; Excluding minor procedures such as diagnostic punctures or infusion device implantation or biliary stenting) or anticipated need for major surgical treatment during the study period; 6. Gastrointestinal abnormalities with obvious clinical manifestations, including but not limited to: intestinal obstruction or the presence of symptoms and signs of intestinal obstruction within 6 months before drug administration, but if the obstruction was completely removed after surgical treatment, screening could be performed (patients with previous intestinal stent implantation and the intestinal stent was not removed during the screening period were not allowed); Patients with gastrointestinal perforation, gastrointestinal fistula, intra-abdominal abscess and non-gastrointestinal fistula (such as tracheoesophageal fistula) within 6 months before administration; Patients with gastrointestinal bleeding (CTCAE≥ grade 3) within 6 months before treatment, or gastrointestinal bleeding (melena, bloody stool, etc.) within 1 month before randomization were eligible if hemorrhoid bleeding was confirmed or only showed positive fecal occult blood.
- 7. Subjects with uncontrolled massive serous effusion or moderate to massive serous effusion requiring repeated drainage (recurrence within 2 weeks after intervention) such as pleural effusion, pericardial effusion, ascites, cachexia, etc.
- 8. Always received including the antibody coupling of topoisomerase inhibitors class I drug therapy, such as DS-8201, HER3-DXd, DS-1062, etc; 9. A history of (noninfectious) interstitial lung disease (ILD) or noninfectious pneumonia requiring steroid therapy, current ILD or noninfectious pneumonia, or ILD or noninfectious pneumonia that could not be ruled out by imaging at screening; 10. Other malignant tumors within 5 years before drug administration, Cured cutaneous squamous cell carcinoma, basal cell carcinoma, non-primary invasive bladder cancer (defined as stage ≤T2a, Gleason score ≤6, and at the time of prostate cancer diagnosis) were excluded Patients with PSA≤10ng/mL (if measured) who had received radical treatment and had no PSA biochemical recurrence could participate in the study), in situ prostate/cervix/breast cancer; 11. Have uncontrolled comorbidities, including but not limited to the following:
- Active HBV or HCV infection Patients with HBsAg (+) and HBV-DNA< 2500 copies /mL or 500 IU/mL were allowed to be enrolled. HCV-Ab (+) and HCV-RNA negative were allowed to enroll.
- HIV infection;
- Known active tuberculosis; Active syphilis;
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- Active or uncontrolled infection requiring systemic anti-infective treatment; Uncontrolled hypertension (systolic blood pressure ≥160mmHg, Diastolic blood pressure > 100 mmHg), symptomatic heart failure (NYHA II-IV), unstable angina or myocardial infarction within 6 months, history of heart failure or systolic dysfunction (LVEF<50%), or risk of QTc prolongation or arrhythmia (baseline QTc>470 msec) ), intractable hypokalemia, long QT syndrome, tachycardia at rest with a heart rate >100 bpm, atrial fibrillation or clinically symptomatic valvular heart disease (if well controlled by treatment), moderate-severe pulmonary hypertension, or a history of other arrhythmias of medical importance).
- Newly diagnosed thromboembolic events requiring treatment within 6 months (patients with well-controlled deep-vein thrombosis of the lower extremities or venous access ports were allowed).
- 12. The toxicity of previous antineoplastic therapy did not recover to CTCAE grade ≤1 (NCI-CTCAE v5.0); Note: Subjects with stable CTCAE grade 2 toxicity related to previous antineoplastic therapy (defined as stable toxicity severity and no CTCAE grade greater than 2 within 3 months before dose administration) could be enrolled, such as: Chemotherapy-induced neurotoxicity, alopecia, skin pigmentation, fatigue, endocrine toxicity caused by previous immunotherapy (such as thyroid dysfunction, diabetes, hyperglycemia, adrenal insufficiency); 13. Previous history of allogeneic bone marrow or organ transplantation; 14. Previous history of allergic reaction or anaphylaxis to antibody drugs; 15. Previous history of severe dry eye, severe meibomian gland disease and/or blepharitis, keratopathy and maculopathy resulting in untreatable or delayed corneal healing of the subject; 16. Pregnant and/or lactating women; 17. Other conditions considered by the investigators to affect the safety or compliance of the study drug treatment, including but not limited to mental disorders, alcohol or drug abuse, etc.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
zhangzhou huang, 13609578088, 1609305255@qq.com
- Recruiting
Sun Yat-sen Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510080
herui yao, 13500018020, yaoherui@163.com
About this study
This is a Phase I open, multi-center, first-in-human study evaluating JSKN016 in subjects with advanced metastatic solid tumors, divided into dose escalation and dose extension.
Read the detailed description
A total of seven (Q3W, the first day of intravenous administration every 3 weeks) dose groups were designed during the dose escalation period. The dose groups were 0.5, 1.0, 2.0, 4.0, 6.0, 7.0 and 8.0 mg/kg, respectively. The DLT observation period was 21 days with accelerated titration BOIN design.
The specific steps for conducting a clinical trial using the BOIN design are as follows:
- The accelerated titration is performed as follows: the first patient is assigned to dose level 1. If this patient does not develop dose-limiting toxicity (DLT), the second patient will be treated at the next higher dose level. Only one patient at a time is treated, and the dose-climbing process continues until the first DLT is observed, or a second grade 2 toxicity is present, or the highest dose is reached, or a Safety Inspection Committee (SMC) discussion decides to end accelerated titration, whichever occurs first. At least two more patients are then treated on the current dose. After that, follow steps 2 and 3 below with at least 3 patients in each group to treat follow-up patients (≥3 patients in the non-accelerated titration dose group).
- Assign the dose to the next group of subjects according to the dose rise and fall rule shown in the Bayesian optimal interval (BOIN). Note the following:
- "Elimination" means the removal of current and higher doses from the trial. The removed dose is a hypertoxic dose and will no longer be used to treat any newly enrolled patients.
- If the current dose is removed, the dose is automatically lowered to the next lower level and administered to the subject for treatment. If the lowest dose is eliminated, the trial is terminated early to ensure subject safety. In this case, the MTD cannot be determined.
- If none of the decision conditions (i.e., raise, lower, or remove the dose) are met, continue to treat the next group (3 subjects) with the current dose.
- If the current dose is the minimum dose but the dose is still required to be reduced by the rules, the new subject is still treated at the current minimum dose. If the number of subjects with DLT reaches the exclusion threshold, the trial is terminated early to ensure subject safety.
- If the current dose is the maximum dose but a higher dose is required by rule, the new subject is treated at the current maximum dose.
- Repeat Step 2 until the set dose escalation phase has a maximum sample size of 20, or the number of evaluable subjects treated at the current dose reaches 9 and the current decision is to maintain the current dose according to the rise and fall rule of the dose escalation decision table.
During dose escalation, the SMC will conduct an ongoing safety assessment. The safety data for each dose group is reviewed by the SMC before the next dose group is administered. For the 6th dose group 7 mg/kg, SMC can decide whether to skip this dose group by comprehensively considering the previous safety, PK and other data. The composition and responsibilities of the SMC will be further detailed in the SMC Constitution.
In each dose group, the administration of the second subject was initiated at least 24 hours after the administration of the first subject to identify some acute toxicities, such as infusion-related reactions.
Allow patients to proceed with intragroup dose escalation to minimize the potential for undertreatment of patients. Intrapatient dose escalation will be performed in the following manner: (1) Intrapatient dose escalation will only be performed if ≤ grade 2 toxicity is observed during the previous treatment cycle; (2) Does not increase to the next higher dose level until the full DLT observation period is evaluated for the next higher dose level and the SMC does not confirm safety concerns; (3) Patients receiving the first dose escalation should be dosed for at least 4 cycles without disease progression. For example, if patients in the 1 mg/kg group completed DLT observation and 4 cycles of dosing, only if patients in the 2 mg/kg cohort completed a complete DLT evaluation, the SMC did not confirm safety concerns, and no grade 2 toxicity was observed in patients in the 1 mg/kg cohort during the previous treatment cycle. Subsequent doses may be increased to 2 mg/kg with the consent of the SMC.
The recommended dose for cohort expansion (RDE) will be determined by the SMC based on safety/tolerability, PK data, and preliminary antitumor activity, as well as other available data. RDE can be at the same dose level as MTD or at a lower dose level than MTD; Rdes may also be different for different indications.
- Conditions
- Advanced Malignant Solid Tumor
- Being tested
- JSKN016 injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JSKN016 injectionDrug
JSKN016 is a bispecific antibody drug conjugate targeting HER3 and TROP2.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation/expansion | Experimental | The subjects at dose escalation stage will be administered with investigational product (JSKN016) starting at 0.5 mg/kg, followed by1 mg/kg，2 mg/kg，4 mg/kg，6 mg/kg，7 mg/kg，8 mg/kgmg/kg, IV ,Q3W The subjects at dose expansion stage will be adiministered with JSKN016 at 6mg/kg or more(anticipated response dose) Receives: Drug: JSKN016 injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs
DLTs are defined as one or more serious toxic reactions that occur within 21 days (Q3W) after the start of dosing and are determined to be reasonably associated with the study drug
Measured: 21 days after the first dose for subjects at dose escalation stage
The frequency and severity of treatment-related adverse events (TEAE), treatment-related adverse events (TRAE), and serious adverse events (SAE).
Clinically significant changes in lab test findings
Measured: From first dose to 30 days after last dose
MTD or RP2D of JSKN 016
To determinate MTD and/ or RP2D of JSKN016
Measured: Postdose of last participant up to 1 year
Objective Response Rate (ORR) in Extended queue
Objective response rate (ORR) was defined as the proportion of participants who achieve either complete response [CR] or partial response [PR] per Response Evaluation Criteria in Solid Tumors (RECIST v1.1）
Measured: Postdose of last participant up to 1 year
Secondary outcomes (6)
Clinical benefit rates (CBR)
Clinical benefit rate (CR+PR+[stable disease (SD) ≥ 6 months]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier.
Measured: Postdose of last participant up to 1 year
Cmax of JSKN016
Maximum (Peak) Observed blood Concentration (Cmax) of JSKN016 Following First Dose
Measured: Predose to 90 days after last dose
Tmax of JSKN016
Time of Maximum blood Concentration (Tmax) of JSKN016 Following First Dose
Measured: Predose to 90 days after last dose
AUC of JSKN016
The blood PK parameters of JSKN016 and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.
Measured: Postdose of last participant up to 1 year
Terminal Elimination Half-life (t1/2)
The blood PK parameters of Terminal elimination half-life for JSKN016
Measured: Postdose of last participant up to 1 year
Duration Of Response (DOR)
Defined as the time from the first evaluation of objective response to the first evaluation of PD or death from any cause prior to PD
Measured: Postdose of last participant up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start30 Apr 2024
- Primary completion17 May 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant Solid TumorStudies of the same condition, open and under way.
- More trials run by Jiangsu Alphamab Biopharmaceuticals Co., LtdThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Sequential Assignment
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Alphamab Biopharmaceuticals Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jieqiong Liu, Principal investigator, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06592417
- Sponsor's protocol ID
- JSKN016-101
- Status last verified
- Apr 2024
- First submitted
- 28 Apr 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors
- ClinicalTrials.gov ID
- NCT06592417
- Acronym / sponsor ID
- JSKN016-101
- Conditions
- Advanced Malignant Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Jiangsu Alphamab Biopharmaceuticals Co., LtdIndustry (pharma, biotech, devices)
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- 17 May 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I open, multi-center, first-in-human study evaluating JSKN016 in subjects with advanced metastatic solid tumors, divided into dose escalation and dose extension.
Detailed description
A total of seven (Q3W, the first day of intravenous administration every 3 weeks) dose groups were designed during the dose escalation period. The dose groups were 0.5, 1.0, 2.0, 4.0, 6.0, 7.0 and 8.0 mg/kg, respectively. The DLT observation period was 21 days with accelerated titration BOIN design.
The specific steps for conducting a clinical trial using the BOIN design are as follows:
- The accelerated titration is performed as follows: the first patient is assigned to dose level 1. If this patient does not develop dose-limiting toxicity (DLT), the second patient will be treated at the next higher dose level. Only one patient at a time is treated, and the dose-climbing process continues until the first DLT is observed, or a second grade 2 toxicity is present, or the highest dose is reached, or a Safety Inspection Committee (SMC) discussion decides to end accelerated titration, whichever occurs first. At least two more patients are then treated on the current dose. After that, follow steps 2 and 3 below with at least 3 patients in each group to treat follow-up patients (≥3 patients in the non-accelerated titration dose group).
- Assign the dose to the next group of subjects according to the dose rise and fall rule shown in the Bayesian optimal interval (BOIN). Note the following:
- "Elimination" means the removal of current and higher doses from the trial. The removed dose is a hypertoxic dose and will no longer be used to treat any newly enrolled patients.
- If the current dose is removed, the dose is automatically lowered to the next lower level and administered to the subject for treatment. If the lowest dose is eliminated, the trial is terminated early to ensure subject safety. In this case, the MTD cannot be determined.
- If none of the decision conditions (i.e., raise, lower, or remove the dose) are met, continue to treat the next group (3 subjects) with the current dose.
- If the current dose is the minimum dose but the dose is still required to be reduced by the rules, the new subject is still treated at the current minimum dose. If the number of subjects with DLT reaches the exclusion threshold, the trial is terminated early to ensure subject safety.
- If the current dose is the maximum dose but a higher dose is required by rule, the new subject is treated at the current maximum dose.
- Repeat Step 2 until the set dose escalation phase has a maximum sample size of 20, or the number of evaluable subjects treated at the current dose reaches 9 and the current decision is to maintain the current dose according to the rise and fall rule of the dose escalation decision table.
During dose escalation, the SMC will conduct an ongoing safety assessment. The safety data for each dose group is reviewed by the SMC before the next dose group is administered. For the 6th dose group 7 mg/kg, SMC can decide whether to skip this dose group by comprehensively considering the previous safety, PK and other data. The composition and responsibilities of the SMC will be further detailed in the SMC Constitution.
In each dose group, the administration of the second subject was initiated at least 24 hours after the administration of the first subject to identify some acute toxicities, such as infusion-related reactions.
Allow patients to proceed with intragroup dose escalation to minimize the potential for undertreatment of patients. Intrapatient dose escalation will be performed in the following manner: (1) Intrapatient dose escalation will only be performed if ≤ grade 2 toxicity is observed during the previous treatment cycle; (2) Does not increase to the next higher dose level until the full DLT observation period is evaluated for the next higher dose level and the SMC does not confirm safety concerns; (3) Patients receiving the first dose escalation should be dosed for at least 4 cycles without disease progression. For example, if patients in the 1 mg/kg group completed DLT observation and 4 cycles of dosing, only if patients in the 2 mg/kg cohort completed a complete DLT evaluation, the SMC did not confirm safety concerns, and no grade 2 toxicity was observed in patients in the 1 mg/kg cohort during the previous treatment cycle. Subsequent doses may be increased to 2 mg/kg with the consent of the SMC.
The recommended dose for cohort expansion (RDE) will be determined by the SMC based on safety/tolerability, PK data, and preliminary antitumor activity, as well as other available data. RDE can be at the same dose level as MTD or at a lower dose level than MTD; Rdes may also be different for different indications.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Sequential Assignment
| Arm | Type | Receives |
|---|---|---|
| Dose escalation/expansion | Experimental | Drug: JSKN016 injectionThe subjects at dose escalation stage will be administered with investigational product (JSKN016) starting at 0.5 mg/kg, followed by1 mg/kg，2 mg/kg，4 mg/kg，6 mg/kg，7 mg/kg，8 mg/kgmg/kg, IV ,Q3W The subjects at dose expansion stage will be adiministered with JSKN016 at 6mg/kg or more(anticipated response dose) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1. Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. The subjects were ≥18 years old on the day of signing the informed consent, male or female; 3. Subjects with histologically and/or cytologically confirmed advanced unresectable or metastatic epithelial malignancies that have failed or are intolerable to previous standard therapies, preferentially but not limited to the following types: AGA-positive non-small cell lung cancer, HER2 IHC 0 breast cancer, etc.
- 4. For AGA-positive NSCLC, the presence of at least one of the following mutations is required; EGFR, ALK, ROS1, NTRK, BRAF V600, MET exon 14, RET, KRAS G12C, or HER2;
- 6. At least one measurable lesion at baseline according to RECIST 1.1 criteria. Measurable disease required either no previous local treatment (e.g., radiotherapy) or evidence of disease progression after local treatment.
- 7. Expected survival time ≥3 months; 8. ECOG score 0 or 1; 9. Female subjects of childbearing potential or male subjects with a fertile partner agreed to use highly effective contraception from the time they provided written informed consent until 24 weeks after the last dose. Female subjects of childbearing potential had to have a negative serum/urine pregnancy test within 7 days before randomization (for women of childbearing age, see Appendix 2).
Key exclusion criteria (9 listed)
- 1. Patients with symptoms of active central nervous system metastases, except those with stable parenchymal brain metastases as assessed by investigators, were defined as seizure-free for more than 12 weeks with or without the use of antiepileptic drugs; No need for glucocorticoids; At least one MRI showed that the patient was stable on imaging. Or stable after treatment for more than 1 month without symptoms; 2. Received any investigational drug within 28 days before dosing; 3. Receipt of other antineoplastic therapy within 28 days before dose or within 5 half-lives of previous antineoplastic drugs, whichever is shorter but requires a minimum of 14 days; Received Chinese herbal medicine with clear anti-tumor indications within 14 days before drug administration; 4. Local palliative treatment within 14 days before administration; 5. Major surgical treatment (such as transabdominal or transthoracic surgery) within 28 days before drug administration; Excluding minor procedures such as diagnostic punctures or infusion device implantation or biliary stenting) or anticipated need for major surgical treatment during the study period; 6. Gastrointestinal abnormalities with obvious clinical manifestations, including but not limited to: intestinal obstruction or the presence of symptoms and signs of intestinal obstruction within 6 months before drug administration, but if the obstruction was completely removed after surgical treatment, screening could be performed (patients with previous intestinal stent implantation and the intestinal stent was not removed during the screening period were not allowed); Patients with gastrointestinal perforation, gastrointestinal fistula, intra-abdominal abscess and non-gastrointestinal fistula (such as tracheoesophageal fistula) within 6 months before administration; Patients with gastrointestinal bleeding (CTCAE≥ grade 3) within 6 months before treatment, or gastrointestinal bleeding (melena, bloody stool, etc.) within 1 month before randomization were eligible if hemorrhoid bleeding was confirmed or only showed positive fecal occult blood.
- 7. Subjects with uncontrolled massive serous effusion or moderate to massive serous effusion requiring repeated drainage (recurrence within 2 weeks after intervention) such as pleural effusion, pericardial effusion, ascites, cachexia, etc.
- 8. Always received including the antibody coupling of topoisomerase inhibitors class I drug therapy, such as DS-8201, HER3-DXd, DS-1062, etc; 9. A history of (noninfectious) interstitial lung disease (ILD) or noninfectious pneumonia requiring steroid therapy, current ILD or noninfectious pneumonia, or ILD or noninfectious pneumonia that could not be ruled out by imaging at screening; 10. Other malignant tumors within 5 years before drug administration, Cured cutaneous squamous cell carcinoma, basal cell carcinoma, non-primary invasive bladder cancer (defined as stage ≤T2a, Gleason score ≤6, and at the time of prostate cancer diagnosis) were excluded Patients with PSA≤10ng/mL (if measured) who had received radical treatment and had no PSA biochemical recurrence could participate in the study), in situ prostate/cervix/breast cancer; 11. Have uncontrolled comorbidities, including but not limited to the following:
- Active HBV or HCV infection Patients with HBsAg (+) and HBV-DNA< 2500 copies /mL or 500 IU/mL were allowed to be enrolled. HCV-Ab (+) and HCV-RNA negative were allowed to enroll.
- Newly diagnosed thromboembolic events requiring treatment within 6 months (patients with well-controlled deep-vein thrombosis of the lower extremities or venous access ports were allowed).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JSKN016 injectionJSKN016 is a bispecific antibody drug conjugate targeting HER3 and TROP2. | Drug | Dose escalation/expansion |
Primary outcome
Incidence of DLTs
Time frame: 21 days after the first dose for subjects at dose escalation stage
DLTs are defined as one or more serious toxic reactions that occur within 21 days (Q3W) after the start of dosing and are determined to be reasonably associated with the study drug
The frequency and severity of treatment-related adverse events (TEAE), treatment-related adverse events (TRAE), and serious adverse events (SAE).
Time frame: From first dose to 30 days after last dose
Clinically significant changes in lab test findings
MTD or RP2D of JSKN 016
Time frame: Postdose of last participant up to 1 year
To determinate MTD and/ or RP2D of JSKN016
Objective Response Rate (ORR) in Extended queue
Time frame: Postdose of last participant up to 1 year
Objective response rate (ORR) was defined as the proportion of participants who achieve either complete response [CR] or partial response [PR] per Response Evaluation Criteria in Solid Tumors (RECIST v1.1）
6 secondary outcomes
Clinical benefit rates (CBR)
Time frame: Postdose of last participant up to 1 year
Cmax of JSKN016
Time frame: Predose to 90 days after last dose
Tmax of JSKN016
Time frame: Predose to 90 days after last dose
AUC of JSKN016
Time frame: Postdose of last participant up to 1 year
Terminal Elimination Half-life (t1/2)
Time frame: Postdose of last participant up to 1 year
Duration Of Response (DOR)
Time frame: Postdose of last participant up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Clinical Experience and Real-world Safety and Effectiveness of Envafolimab: Patient Access Program
Advanced Solid Tumor
Active, not recruitingPhase 2
Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jieqiong Liu principal investigator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JSKN016 injection in people with Advanced Malignant Solid Tumor, run by Jiangsu Alphamab Biopharmaceuticals Co., Ltd at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact herui yao yaoherui, D.PH (13500018020, yaoherui@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of DLTs (time frame: 21 days after the first dose for subjects at dose escalation stage). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.