Malignant NeoplasmPhase 1/2NCT06385925
A Study of TSN1611 Treating Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
A Phase 1/2 study testing TSN1611 in people with Malignant Neoplasm, run by Tyligand Pharmaceuticals (Suzhou) Limited at 19 sites in 2 countries.
Trial summary
The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Malignant Neoplasm
- What is being tested?
- TSN1611
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 440 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 29 Apr 2024to 30 Apr 2027
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Subjects will be excluded if they meet any of the following criteria:
- Leptomeningeal disease or Active central nervous system (CNS) metastases.
- Prior systemic anti-cancer treatment within 21 days or 5 half-lives (whichever is shorter will be used as the criteria) prior to the first dose of study drug.
- Radical radiation within 4 weeks prior to the first dose of study drug; palliative radiotherapy within 1 week prior to the first dose of study drug.
- Any unresolved Grade 2 or higher toxicity from previous anticancer therapy except alopecia.
- Has participated in a study of investigational agent and received the investigational agent within 21 days or 5 half-lives, if known (whichever is shorter) prior to the first dose of study drug.
Show all 10Show fewer
- History of interstitial lung disease (ILD), drug induced IDL, or current active pneumonitis, radiation pneumonitis requiring therapeutic intervention, or uncontrolled other lung disease.
- Any of the following in the past 6 months: myocardial infarction, unstable angina, symptomatic congestive heart failure, stroke or transient ischemic attack, pulmonary embolism.
- Prior treatment with KRAS G12D targeted therapy.
- Has a history or current evidence of any severe condition, concurrent therapy, or laboratory abnormality that might confound the interpretation of the study results, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the investigator.
Trial locations and contacts
19 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
19 sites in 2 countries
China16 sites, 16 recruiting
- Recruiting
Beijing Cancer Hospital
Beijing, Beijing Municipality
Minglei Zhuo
Minglei Zhuo
- Recruiting
Beijing Cancer Hospital, Beijing, China
Beijing, 100142
Lin Shen
Lin Shen, MD
- Recruiting
Hunan Cancer Hospital
Changsha, Hunan
Lin Wu, MD
Lin Wu
- Recruiting
West China Hospital, Sichuan University
Chengdu, Sichuan
Ma Ji
Ji Ma
- Recruiting
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong
Chengzhi Zhou
Chengzhi Zhou
- Recruiting
Sir Run Run Shaw Hospital - Zhejiang University School of Med
Hangzhou, Zhejiang
Haizhou Lou
Haizhou Lou
- Recruiting
The First Affiliated Hospital - Zhejiang University School of Medicine
Hangzhou, Zhejiang
Jianya Zhou
Jianya Zhou
- Recruiting
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang
Yuan Ying
Ying Yuan
- Recruiting
Anhui Provincial Cancer Hospital
Hefei, Anhui
Yueyin Pan
Yueyin Pan
- Recruiting
Linyi Cancer Hospital
Linyi, Shandong
Janhua Shi
Jianhua Shi
- Recruiting
The First Affiliated Hospital of Nanchang University - Donghu District
Nanchang, Jiang
Yong Li
Pu Li
- Recruiting
Shanghai Tenth People's Hospital
Shanghai, Shanghai Municipality
Xiaojun Chen
Xiaojun Chen
- Recruiting
Shanghai Chest Hospital, Shanghai, China
Shanghai, 200030
Shun Lu
Shun Lu, MD
- Recruiting
Shanghai Zhongshan Hospital, Shanghai, China
Shanghai, 200032
Tianshu Liu
Tianshu Liu, MD
- Recruiting
Taizhou Hospital of Zhejiang Province
Taizhou, Zhejiang
Dongqing Lv
Dongqing Lv
- Recruiting
Hubei Cancer Hospital
Wuhan, Hubei
Bin Yang
Bin Yang
United States3 sites, 3 recruiting
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
Alexander Spira, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Siqing Fu, MD,PhD
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
David Sommerhalder, MD
About this study
Official title: Phase 1/2 Study of TSN1611 in Subjects With Advanced Solid Tumors Harboring KRAS G12D Mutation
The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part. This study will evaluate the efficacy of TSN1611 at RP2D(s) through ORR using RECIST version 1.1, and determine and confirm the MTD/RP2D for TSN1611 in combination with cetuximab, in combination with cetuximab and mFOLFOX6, in combination with gemcitabine and albumin-bound paclitaxel in subjects with selected solid tumors.
Read the detailed description
Phase 1 Part of TSN1611 Monotherapy:
The phase 1 part will evaluate the prespecified dose levels of TSN1611. Dose escalation will continue until up to the highest planned dose or the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. Dose optimization could be performed as indicated by the emerging data.
Phase 2 Part of TSN1611 Monotherapy:
hase 2 part of TSN1611 monotherapy will evaluate the efficacy and safety of TSN1611 as monotherapy at the RP2D until disease progression or unacceptable toxicity in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations.
Phase 1b/2 Part of TSN1611 Combination Therapy:
This part will consist of the investigations of 3 combined therapies (Cohort A, B and C). In each cohort, there will be a Phase 1b Safety Lead-in Stage to determine the dose of TSN1611 for the combination therapy (this part will be conducted in selected sites), followed by the Phase 2 Expansion Stage to enroll more subjects to determine the efficacy in different cohorts.
- Conditions
- Malignant Neoplasm
- Being tested
- TSN1611
- Keywords
- solid tumor, KRAS G12D mutation, pancreatic cancer, colorectal cancer, non-small cell lung cancer, malignant neoplasm
- Medical subject headings
- Neoplasms, Pancreatic Neoplasms, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TSN1611Drug
TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.
TSN1611Drug
TSN1611 BID, Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.
TSN1611Drug
Also called Paclitaxel (albumin-bound)
TSN1611 BID, Paclitaxel (albumin-bound) at 125 mg/m² and gemcitabine at 1000 mg/m² will be administered via intravenous infusion on Days 1, 8, and 15 of each 4-week cycle.
TSN1611Drug
Also called Oxaliplatin injection, fluorouracil, leucovorin
TSN1611 BID everyday and Patients will be administered with mFOLFOX6 on Days 1 and 2, every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Dose-finding/evaluation of TSN1611 monotherapy | Experimental | The phase 1 part will evaluate the prespecified sequential dose levels of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors to determine the recommended dose of TSN1611 for further investigation. Receives: Drug: TSN1611 |
| Phase 2: Dose expansion of TSN1611 monotherapy | Experimental | Phase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose level in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations. Receives: Drug: TSN1611 |
| Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort A | Experimental | Cohort A: TSN1611 combined with cetuximab treating subjects with advanced solid tumors harboring KRAS G12D mutation: Receives: Drug: TSN1611 |
| Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort B | Experimental | Cohort B: TSN1611 combined with GnP regimen (i.e., gemcitabine and nab-paclitaxel) treating subjects with advanced PDAC with KRAS G12D mutation who received no prior systemic treatment in the advanced setting. Receives: Drug: TSN1611 |
| Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort C | Experimental | Cohort C: TSN1611 combined with cetuximab and mFOLFOX6 regimen (i.e., fluorouracil, leucovorin, oxaliplatin) treating subjects with advanced CRC with KRAS G12D mutation who received no prior systemic treatment in the advanced setting. Receives: Drug: TSN1611 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs) in phase 1 part
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D[s]) of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.
Measured: 21 days
Objective response rate (ORR) in phase 2 part
To evaluate the anti-tumor activity of TSN1611 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: Up to 3 years
Secondary outcomes (9)
Adverse events
To assess the safety profile and tolerability of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.
Measured: Up to 3 years
Area under the plasma concentration-time curve (AUC)
To characterize the pharmacokinetic (PK) profile of TSN1611.
Measured: 9 weeks
Maximum blood concentrations (Cmax)
To characterize the PK profile of TSN1611.
Measured: 9 weeks
Time to maximum blood concentration (Tmax)
To characterize the PK profile of TSN1611.
Measured: 9 weeks
Duration of response (DOR)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Measured: Up to 3 years
Time to response (TTR)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Measured: Up to 3 years
Disease control rate (DCR)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Measured: Up to 3 years
Progression free survival (PFS)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Measured: Up to 3 years
Overall survival
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2024
- Study start29 Apr 2024
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant NeoplasmStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tyligand Pharmaceuticals (Suzhou) Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cindy Li, Study director, Tyligand Bioscience (Shanghai) Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06385925
- Sponsor's protocol ID
- TSN1611-2023-101
- Status last verified
- Apr 2026
- First submitted
- 18 Apr 2024
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study of TSN1611 in Subjects With Advanced Solid Tumors Harboring KRAS G12D Mutation
- ClinicalTrials.gov ID
- NCT06385925
- Acronym / sponsor ID
- TSN1611-2023-101
- Conditions
- Malignant Neoplasm
- Keywords
- solid tumor, KRAS G12D mutation, pancreatic cancer, colorectal cancer, non-small cell lung cancer, malignant neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 440 participants (estimated)
- Lead sponsor
- Tyligand Pharmaceuticals (Suzhou) LimitedIndustry (pharma, biotech, devices)
- Study start
- 29 Apr 2024 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 26 Apr 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.
The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part. This study will evaluate the efficacy of TSN1611 at RP2D(s) through ORR using RECIST version 1.1, and determine and confirm the MTD/RP2D for TSN1611 in combination with cetuximab, in combination with cetuximab and mFOLFOX6, in combination with gemcitabine and albumin-bound paclitaxel in subjects with selected solid tumors.
Detailed description
Phase 1 Part of TSN1611 Monotherapy:
The phase 1 part will evaluate the prespecified dose levels of TSN1611. Dose escalation will continue until up to the highest planned dose or the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. Dose optimization could be performed as indicated by the emerging data.
Phase 2 Part of TSN1611 Monotherapy:
hase 2 part of TSN1611 monotherapy will evaluate the efficacy and safety of TSN1611 as monotherapy at the RP2D until disease progression or unacceptable toxicity in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations.
Phase 1b/2 Part of TSN1611 Combination Therapy:
This part will consist of the investigations of 3 combined therapies (Cohort A, B and C). In each cohort, there will be a Phase 1b Safety Lead-in Stage to determine the dose of TSN1611 for the combination therapy (this part will be conducted in selected sites), followed by the Phase 2 Expansion Stage to enroll more subjects to determine the efficacy in different cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Dose-finding/evaluation of TSN1611 monotherapy | Experimental | Drug: TSN1611The phase 1 part will evaluate the prespecified sequential dose levels of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors to determine the recommended dose of TSN1611 for further investigation. |
| Phase 2: Dose expansion of TSN1611 monotherapy | Experimental | Drug: TSN1611Phase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose level in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations. |
| Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort A | Experimental | Drug: TSN1611Cohort A: TSN1611 combined with cetuximab treating subjects with advanced solid tumors harboring KRAS G12D mutation: |
| Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort B | Experimental | Drug: TSN1611Cohort B: TSN1611 combined with GnP regimen (i.e., gemcitabine and nab-paclitaxel) treating subjects with advanced PDAC with KRAS G12D mutation who received no prior systemic treatment in the advanced setting. |
| Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort C | Experimental | Drug: TSN1611Cohort C: TSN1611 combined with cetuximab and mFOLFOX6 regimen (i.e., fluorouracil, leucovorin, oxaliplatin) treating subjects with advanced CRC with KRAS G12D mutation who received no prior systemic treatment in the advanced setting. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Leptomeningeal disease or Active central nervous system (CNS) metastases.
- Prior systemic anti-cancer treatment within 21 days or 5 half-lives (whichever is shorter will be used as the criteria) prior to the first dose of study drug.
- Radical radiation within 4 weeks prior to the first dose of study drug; palliative radiotherapy within 1 week prior to the first dose of study drug.
- Any unresolved Grade 2 or higher toxicity from previous anticancer therapy except alopecia.
- Has participated in a study of investigational agent and received the investigational agent within 21 days or 5 half-lives, if known (whichever is shorter) prior to the first dose of study drug.
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 |
|---|---|---|
| TSN1611TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity. | Drug | Phase 1: Dose-finding/evaluation of TSN1611 monotherapy, Phase 2: Dose expansion of TSN1611 monotherapy |
| TSN1611TSN1611 BID, Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks. | Drug | Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort A |
| TSN1611Also: Paclitaxel (albumin-bound)TSN1611 BID, Paclitaxel (albumin-bound) at 125 mg/m² and gemcitabine at 1000 mg/m² will be administered via intravenous infusion on Days 1, 8, and 15 of each 4-week cycle. | Drug | Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort B |
| TSN1611Also: Oxaliplatin injection, fluorouracil, leucovorinTSN1611 BID everyday and Patients will be administered with mFOLFOX6 on Days 1 and 2, every 2 weeks. | Drug | Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort C |
Primary outcome
Dose limiting toxicities (DLTs) in phase 1 part
Time frame: 21 days
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D[s]) of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.
Objective response rate (ORR) in phase 2 part
Time frame: Up to 3 years
To evaluate the anti-tumor activity of TSN1611 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
9 secondary outcomes
Adverse events
Time frame: Up to 3 years
Area under the plasma concentration-time curve (AUC)
Time frame: 9 weeks
Maximum blood concentrations (Cmax)
Time frame: 9 weeks
Time to maximum blood concentration (Tmax)
Time frame: 9 weeks
Duration of response (DOR)
Time frame: Up to 3 years
Time to response (TTR)
Time frame: Up to 3 years
Disease control rate (DCR)
Time frame: Up to 3 years
Progression free survival (PFS)
Time frame: Up to 3 years
Overall survival
Time frame: Up to 3 years
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 24 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Cindy Li study director
Tyligand Bioscience (Shanghai) Limited
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TSN1611 in people with Malignant Neoplasm, run by Tyligand Pharmaceuticals (Suzhou) Limited at 19 sites in 2 countries.
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 0 inclusion and 10 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 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in China, United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Tyligand Clinical Trial Info (+86 021-50720081, clinical_trial@tyligand.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities (DLTs) in phase 1 part (time frame: 21 days). The study lists 2 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 24 Apr 2026.