It's a dose escalation to identify the Maximum Tolerated dose (MTD) , recommended dose for expansion (RDE) or recommended Phase II dose (RP2D) of JSKN003, guided by the modified ADT design and BOIN design.

JSKN003 is to be administered via intravenous (IV) dose

JSKN003

Jeannette Devoto

Silvie Radmil

Arlene Chan

This study is an open-label, multicenter, first-in-human, Phase I, dose escalation study to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of JSKN003 in subjects with advanced inoperable or metastatic solid malignant tumors that are expected to be HER2 expression.

The dose escalation study will utilize single patient accelerated dose titration for the first two dose levels, 1.0 and 2.1 mg/kg, followed by dose cohorts 4.2, 5.2, 6.3, 7.3, and 8.4 mg/kg which will all be enrolled and monitored using the Bayesian optimal interval design, aimed at determining the MTD, RDE/RP2D of JSKN003. The dose-escalation of 9.4 mg/kg and 10.5 mg/kg should be determined per discussion between Safety Monitoring Committee and sponsor if deemed necessary, the SMC had the right of deciding to dose-escalate at other dose levels . Moreover, the SMC is also responsible for deciding the MTD and the recommended dose level for dose-expansion study.

Enrolled patients will be sequentially assigned to the planned dose levels as required by the protocol and treated with JSKN003 IV Q3W to observe the occurrence of treatment related AEs and dose limiting toxicities. The DLT observation period is 21 days from administration of the first dose of JSKN003.

The study will use a modified ADT design and BOIN design for dosing cohort management to determine the MTD and RDE/RP2D. The starting dose of JSKN003 is 1.0 mg/kg, followed by 2.1, 4.2, 5.3, 6.3, 7.3, 8.4, 9.4 and 10.5 mg/kg. The investigational product will be administered on Day 1 every 3 weeks via intravenous infusion, and the first cycle of JSKN003 treatment is for DLT evaluation.

The starting dose of JSKN003 is 1.0 mg/kg, followed by 2.1, 4.2, 5.3, 6.3, 7.3, 8.4, 9.4 and 10.5 mg/kg.

First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors

A Phase I, Multi-center, Open-label, Dose Escalation, First-In-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of JSKN003 in Subjects With Advanced or Metastatic Solid Malignant Tumors

recommended dose for expansion / recommended phase 2 dose

Incidence and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs)

Maximum (Peak) Observed blood Concentration (Cmax) of JSKN003 Following First Dose

Time of Maximum blood Concentration (Tmax) of JSKN003 Following First Dose

The blood PK parameters of JSKN003 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.

The blood PK parameters of Terminal elimination half-life for JSKN003

Objective response rate (ORR) by independent central review 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.

TTR is defined as the time from the date of first study dose to the date of earliest qualifying response

Duration of response for responders (CR or PR) is defined as the time interval between the date of earliest qualifying response and the date of PD or death for any cause, whichever occurs earlier.

PFS is defined as the time from the date of first study dose to disease progression or death whichever occurs first. Subjects without event (no disease progression or alive at last visit) will be censored at the date of "last tumor assessment".

Status (positive or negative) and serum titers of anti-JSKN003 antibody

Alphamab (Australia) Co Pty Ltd.

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Capecitabine

Vinorelbine

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Administered intravenously according to protocol.

The mono-chemotherapy drugs selected by the investigators included capecitabine, gemcitabine, vinorelbine, docetaxel, albumin-bound paclitaxel, or eribulin. The option should be determined before randomization.

Administered according to protocol, as one option for investigator's choice (determined before randomization).

Capecitabine tablets

Gemcitabine hydrochloride for injection

Vinorelbine tartrate injection

Paclitaxel for injection (albumin-bound type)

Docetaxel injection

Eribulin mesylate injection

Erwei Song

Jiong Wu

Jing Sun

Hua Yang

Dong Yan

Weihong Zhao

Jiuwei Cui

Ying Liu

Shouman Wang

Ting Luo

Xianjun Tang

Lu Gan

man Li

Fan Wu

Ning Liao

Jieqiong Liu

Shusen Wang

Qingyuan Zhang

Xian Wang

Peifen Fu

Jian Huang

Hai Hu

yueyin Pan

Jiqing Hao

Fufan Li

Jianyun Nie

Yingxia Tian

Jingfen Wang

Guixiang Weng

Zhongmin Zhang

Yongmei Yin

Weimin Xie

weimin Xie

Li Nong

Yanyan Xie

Wenfeng Li

Jian Zhang

De Zen

Guoqin Jiang

Jinnan Gao

Fuguo Tian

Feng Yao

Yanxia Zhao

Hanjun Yu

Jin Yang

Yuehua Wang

Zhengqiu Zhu

Hong Zong

This study is a randomized controlled, open-label, multicenter phase III clinical study evaluating the efficacy and safety of chemotherapy selected by investigator JSKN003 s in subjects with recurrent or metastatic breast cancer who have previously failed first- or second-line chemotherapy in subjects with recurrent or metastatic breast cancer who have failed prior first- or second-line chemotherapy.

The study planned to enroll 400 subjects in a 1:1 ratio and stratified block randomization method assigned to:

* Experimental group: JSKN003 monotherapy
* Control group: investigator's chosen chemotherapy drug (capecitabine, gemcitabine, vinorelbine, docetaxel, albumin-bound paclitaxel, or eribulin) monotherapy

This study is a randomized controlled, open-label, multicenter phase III clinical study evaluating the efficacy and safety of chemotherapy selected by investigator JSKN003 s in subjects with recurrent or metastatic breast cancer who have previously failed first- or second-line chemotherapy in subjects with recurrent or metastatic breast cancer who have failed prior first- or second-line chemotherapy.

The study planned to enroll 400 subjects in a 1:1 ratio and stratified block randomization method assigned to:

* Experimental group: JSKN003 monotherapy
* Control group: investigator's chosen chemotherapy drug (capecitabine, gemcitabine, vinorelbine, docetaxel, albumin-bound paclitaxel, or eribulin) monotherapy.

A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial

JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial Of JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

PFS evaluated by BICR according to RECIST v1.1 criteria is defined as the time from randomization to the first recorded disease progression or death from any cause as a result of BICR evaluation according to RECIST v1.1 criteria.

OS, defined as the time from randomization to death from any cause;

BICR and investigators were judged according to RECIST v1.1 criteria ，objective response rate (ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria;

BICR and investigators were judged according to RECIST v1.1 criteria，Duration of response (DoR), defined as the time from the first recorded response (CR/PR) to the first documented disease progression (PD) or death from any cause;

Jiangsu Alphamab Biopharmaceuticals Co., Ltd

in dose escalation and expansion period，total 9 dose groups were designed. Subjects will be give dose 1.0, 2.1, 4.2, 5.3, 6.3, 7.3, 8.4, 9.4 and 10.5 mg/kg Q3W based on DLT results.

JSKN003 should be given on the first day of administration every 3 weeks by intravenous drip.

jian zhang

Lin Shen

Banwei Cao

Dihong Tang

An Lin

Qunxian Rao

Chunyan Lan

Jian Ruan

Xiaochen Zhang

Yaqing Chen

Jieer Ying

Yueying Pan

Bo Liu

Zhen Li

Xinshuai Wang

Anwen Liu

Jia Wei

Bo Shen

Yongqian Su

Li Li

Lei Yang

Xiaohua Wu

Gang Jin

jian zhang, professor

Qun Li

Zhixiang Zhuang

Jing Dai

Xiang Wang

Hong Zhong

This is an open, multicenter study of stage I/II in Chinese subjects with unresectable locally advanced/metastatic solid tumors. It is divided into dose escalation period and cohort expansion period. A total of 9 dose groups (Q3W on the first day of intravenous administration every three weeks) were designed in the dose escalation period. The initial dose was 1.0mg/kg, Q3W, and the observation period of DLT was 21 days. In the dose expansion phase, 5 cohorts were set up.

A total of nine (Q3W, the first day of intravenous administration every three weeks) dose groups were designed in the dose escalation period. The dose groups were 1.0, 2.1, 4.2, 5.3, 6.3, 7.3, 8.4, 9.4 and 10.5 mg/kg, respectively. The BOIN design with accelerated titration was used, and the DLT observation period was 21 days.

The specific steps for conducting a clinical trial using the BOIN design are as follows:

1. Perform the accelerated titration as follows: Assign the first patient 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. Treat one patient at a time and continue the dose-climbing process until the first DLT is observed, or a second grade 2 toxicity occurs, or the highest dose is reached. Two more patients were then treated on the current dose. After that, follow steps 2 and 3 and take the number of cases in each group as 3 to treat the follow-up patients.
2. Assign the dose to the next group of subjects according to the dose rise and fall rule shown in the Bayesian Optimal interval (BOIN) decision table.
3. Repeat Step 2 until the set maximum sample size of 45 or the number of evaluable subjects treated at the current dose reaches 12 and the current decision is to maintain the current dose according to the rise and fall rule of the dose rise and fall decision table.

After the dose escalation period was completed, order preserving regression was used to determine MTD. Once MTDS have been identified and the maximum sample size of 45 patients has not been reached, sponsors may enroll up to 12 additional patients in the selected MTDS to obtain more information on the safety and efficacy of the selected dose. In the additional extension process, the cull boundary in the decision table is used for toxicity monitoring.

The Safety Monitoring Committee (SMC) will conduct an ongoing safety assessment during the dose escalation period. The safety data of each dose group should be reviewed and decided by the SMC before starting the administration of the next dose group. If additional safety, efficacy, and PK data are required for a dose group by SMC resolution, subjects will be allowed to continue to be enrolled in this dose group after completing the BOIN dose increment; If the SMC has decided that a dose group can proceed to the cohort extension phase, it is permitted to proceed directly to the cohort extension phase in that dose group (i.e. to Phase Ib). The composition and responsibilities of the SMC will be further detailed in the SMC Constitution.

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.

To Evaluate the Safety and Tolerability of JSKN003 in Chinese Subjects With Advanced Solid Tumors

Phase I/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of JSKN003 in Chinese Subjects With Advanced Solid Tumors

Incidence of dose-limiting toxicity (DLT) in dose esclation period

MTD (Maximum tolerated Dose) is the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate based on the BOIN Design

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）

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.

PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors	NCT05494918	Advanced Solid ... Metastatic Soli...	JSKN003	18 Years -	Alphamab (Australia) Co Pty Ltd.
JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects	NCT06079983	Breast Cancer	JSKN003 Capecitabine ta... Gemcitabine hyd... Vinorelbine tar... Paclitaxel for ... Docetaxel injec... Eribulin mesyla...	18 Years -	Jiangsu Alphamab Biopharmaceuticals Co., Ltd
To Evaluate the Safety and Tolerability of JSKN003 in Chinese Subjects With Advanced Solid Tumors	NCT05744427	Advanced Solid ...	JSKN003	18 Years -	Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Spots Global Cancer Trial Database for jskn003

Every month we try and update this database with for jskn003 cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for jskn003

Every month we try and update this database with for jskn003 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for jskn003 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.