HER2-Expressing Advanced Solid TumorsPhase 1NCT07922096
A First-in-human Study of SMP-656 in Subjects With Locally Advanced/ Metastatic HER2 Expressing or Mutated Solid Tumors
A Phase 1 study testing SMP-656 Injection in people with HER2-Expressing Advanced Solid Tumors and HER2-Mutated Advanced Solid Tumors, run by Chengdu SciMount Pharmatech Co., Ltd. at 5 sites in China.
Trial summary
This is an open-label, first-in-human (FIH), phase 1 dose-escalation and cohort expansion study of SMP-656 in subjects with locally advanced/metastatic HER2 expressing or HER2-mutated solid tumors. The study consists of 2 parts: dose-escalation (Part 1) and cohort expansion (Part 2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-Expressing Advanced Solid Tumors, HER2-Mutated Advanced Solid Tumors, Metastatic Solid Tumors
- What is being tested?
- SMP-656 Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 5 sitesChina
- Study dates
- 1 Feb 2024to 30 Apr 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Voluntarily participate in this clinical trial, understand and comply with study procedures, and provide written informed consent voluntarily.
- Male or female; aged >= 18 years at the time of signing the informed consent form.
- Expected survival >= 12 weeks.
- Histologically or cytologically confirmed HER2-expressing or HER2-mutated advanced solid tumors .
- In the dose-expansion stage, patients must additionally meet the requirements of one of the following cohorts: (1) HER2-positive or HER2-low breast cancer; (2) HER2-mutated or -amplified NSCLC ; (3) Other HER2-positive or HER2-mutated solid tumors.
- Have at least 1 measurable target lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
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- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Adequate bone marrow, hepatic, renal and coagulation function based on laboratory tests performed within 7 days before the first dose.
- Women of childbearing potential (WOCBP) must agree to use highly effective contraception or maintain abstinence from the time of informed consent signature through 7 months after the last administration of the investigational product; serum pregnancy testing performed within 7 days before the first dose must be negative. Male patients of childbearing potential must agree to use highly effective contraception and not to donate sperm during the same period.
Who cannot join
- Insufficient washout of prior antitumor therapy before the first dose: chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives (whichever is shorter); antibody therapy within 3 weeks; hormonal therapy within 2 weeks; antitumor Chinese patent medicine within 2 weeks; palliative radiotherapy within 2 weeks; radical radiotherapy within 4 weeks; nitrosoureas or mitomycin within 6 weeks; major surgery within 28 days; any other investigational antitumor agent within 28 days.
- Have received eribulin or an eribulin-containing ADC in prior lines of therapy.
- Known history of severe hypersensitivity to inetetamab, SMP-656 or any of their excipients.
- Prior anti-tumor treatment-related toxicities (alopecia excluded) that remain at Grade > 1 or have not recovered to baseline, except adverse events deemed by the Investigator not to pose a safety risk.
- Grade >= 2 peripheral neuropathy, or prior history of Grade >= 3 neurotoxicity/peripheral neuropathy, or permanent discontinuation of previous antitumor treatment due to neurotoxicity or peripheral neuropathy.
- Uncontrollable pleural effusion, pericardial effusion or ascites.
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- Diabetes mellitus that remains uncontrolled despite optimal supportive care.
- Previous, current or suspected interstitial lung disease (ILD), drug-induced ILD, or clinically significant active pneumonia identified at screening, or radiation pneumonitis, or other severe pulmonary disorders impairing respiratory function which, in the Investigator's judgment, may interfere with the detection or management of investigational product-related pulmonary toxicity.
- Primary central nervous system (CNS) tumors, meningeal metastases, or active CNS metastases that have failed local treatment.
- Any other malignancy (other than the study tumor type) diagnosed within 5 years before the first dose, except curatively treated localized malignancies such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, papillary thyroid carcinoma or ductal carcinoma in situ of the breast.
- Pre-existing autoimmune disease requiring systemic treatment (excluding corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency).
- History of allogeneic stem cell transplantation or solid organ transplantation, or planned allogeneic stem cell transplantation or solid organ transplantation during the study.
- Current drug-induced liver injury, autoimmune liver disease , persistent extrahepatic obstruction caused by gallstones, cirrhosis or portal hypertension.
- Clinically significant history of cardiovascular disease,.
- Active infection, including clinically uncontrolled active infectious disease such as acute pneumonia or persistent fever of unknown origin within 7 days before the first dose.
- Pregnancy or lactation.
- Any concurrent uncontrolled disease that, in the Investigator's judgment
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Beijing Cancer Hospital
Beijing, Beijing Municipality
Jilin Cancer Hospital
Changchun, Jilin
Fujian Cancer Hospital
Fuzhou, Fujian
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality
About this study
Official title: A Phase I, Two-Part, Open-Label, Multicenter Study of SMP-656 in Subjects With Locally Advanced/Metastatic HER2 Expressing or HER2-Mutated Solid Tumors to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor.
This is an open-label, first-in-human (FIH), phase 1 dose-escalation and cohort expansion study of SMP-656 in subjects with locally advanced/metastatic HER2 expressing or HER2-mutated solid tumors. The study consists of 2 parts: dose-escalation (Part 1) and cohort expansion (Part 2). Part 1 consists of dose escalation cohorts for determining the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Part 2 consists of expansion cohorts, including but not limited to breast cancer, non-small cell lung cancer, gynecologic, gastrointestinal and other solid tumors.
A total of 35 participants were enrolled between February 2024 and April 2026. The trial has been completed.
Read the detailed description
This was a first-in-human, open-label, multicenter Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity of SMP-656, in patients with locally advanced/metastatic HER2 expressing or HER2-mutated solid tumors.
The trial enrolled 35 participants at five sites in China.
Dose-escalation stage: SMP-656 was administered by intravenous infusion once every 3 weeks (Q3W; each 21-day period was one treatment cycle) using a classical 3+3 design.
Dose-expansion stage: participants were enrolled and treated Q3W at the dose level(s) selected from dose escalation.
- Conditions
- HER2-Expressing Advanced Solid Tumors, HER2-Mutated Advanced Solid Tumors, Metastatic Solid Tumors
- Being tested
- SMP-656 Injection
- Keywords
- SMP-656, Phase I, Advanced Solid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SMP-656 InjectionDrug
Also called SMP-656
SMP-656 was supplied as a 50 mg/vial injection for intravenous infusion and given Q3W at 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 mg/kg during dose escalation and at the selected dose level(s) during dose expansion. Treatment continues until disease progression, intolerable toxicity, voluntary withdrawal, death or trial termination.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose-escalation six doses levels have been selected for evaluation | Experimental | SMP-656 administered intravenously once every 3 weeks (Q3W) Receives: Drug: SMP-656 Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose-Limiting Toxicity (DLT)
Number and percentage of participants who experienced a protocol-defined DLT during the 21-day DLT observation period after the first SMP-656 infusion, graded according to NCI CTCAE v5.0 (hematologic, hepatic and non-hematologic/non-hepatic toxicities).
Measured: 21 days after the first dose of SMP-656
Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D)
The MTD and/or RP2D of SMP-656 determined from the integrated analysis of DLT, safety, pharmacokinetic and preliminary antitumor activity data across the five dose levels evaluated (0.5, 1.0, 1.5, 2.0 and 2.5 mg/kg).
Measured: Through study completion, up to 27 months from first dose
Secondary outcomes (9)
Objective Response Rate (ORR) Assessed by Investigators
ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of complete response (CR) or partial response (PR) per RECIST v1.1.
Measured: From the date of first dose to the date of first radiological documentation of disease progression or death, whichever occurs first (up to 27 months)
Duration of Response (DOR)
DOR is the time from the date of first documented confirmed objective response (CR or PR per RECIST v1.1) until the date of disease progression or death.
Measured: From first confirmed objective response (CR/PR) up to 27 months from first dose
Progression-Free Survival (PFS)
PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).
Measured: From the date of first dose to the date of first radiological documentation of disease progression or death, whichever occurs first (up to 27 months)
1-Year Overall Survival Rate
Proportion of participants alive 1 year after the first dose of SMP-656.
Measured: 1 year after the first dose
Area Under the Concentration Versus Time Curve (AUC) of Serum SMP-656 Following First Dose
The serum PK parameters of SMP-656 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: Post first dose up to 2 years
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum SMP-656 Following First Dose
The serum PK parameters Maximum (peak) Observed serum concentration of SMP-656 and its analytes were estimated using standard non-compartmental method.
Measured: Post first dose up to 2 years
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum SMP-656 Following First Dose
The serum PK parameters of Time of maximum plasma concentration (Tmax) for SMP-656 and its analytes were estimated using standard non-compartmental methods.
Measured: Post first dose up to 2 years
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of SerumSMP-656 Following First Dose
The serum PK parameters of Terminal elimination half-life forSMP-656 and its analytes was estimated using standard non-compartmental methods.
Measured: Post first dose up to 2 years
Overview of Treatment-emergent Adverse Events
Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Event
Measured: Baseline up to 28 days after the last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2026
- Study start1 Feb 2024
- Primary completion30 Apr 2026
- Study completion30 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-Expressing Advanced Solid TumorsStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- open-label first-in-human trial with a dose-escalation stage (classical 3+3 design; 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mg/kg Q3W; ) followed by a dose-expansion stage at the dose level(s) selected from escalation.
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chengdu SciMount Pharmatech Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jian Zhang, MD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07922096
- Sponsor's protocol ID
- SMP-656-101
- Other IDs
- CTR20233290, 2023LP01663
- Status last verified
- Nov 2026
- First submitted
- 1 Nov 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Two-Part, Open-Label, Multicenter Study of SMP-656 in Subjects With Locally Advanced/Metastatic HER2 Expressing or HER2-Mutated Solid Tumors to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor.
- ClinicalTrials.gov ID
- NCT07922096
- Acronym / sponsor ID
- SMP-656-101
- Conditions
- HER2-Expressing Advanced Solid Tumors, HER2-Mutated Advanced Solid Tumors, Metastatic Solid Tumors
- Keywords
- SMP-656, Phase I, Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Chengdu SciMount Pharmatech Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- 30 Apr 2026 (actual)
- Study completion
- 30 Apr 2026 (actual)
- First posted
- 6 Nov 2026 (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 an open-label, first-in-human (FIH), phase 1 dose-escalation and cohort expansion study of SMP-656 in subjects with locally advanced/metastatic HER2 expressing or HER2-mutated solid tumors. The study consists of 2 parts: dose-escalation (Part 1) and cohort expansion (Part 2). Part 1 consists of dose escalation cohorts for determining the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Part 2 consists of expansion cohorts, including but not limited to breast cancer, non-small cell lung cancer, gynecologic, gastrointestinal and other solid tumors.
A total of 35 participants were enrolled between February 2024 and April 2026. The trial has been completed.
Detailed description
This was a first-in-human, open-label, multicenter Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity of SMP-656, in patients with locally advanced/metastatic HER2 expressing or HER2-mutated solid tumors.
The trial enrolled 35 participants at five sites in China.
Dose-escalation stage: SMP-656 was administered by intravenous infusion once every 3 weeks (Q3W; each 21-day period was one treatment cycle) using a classical 3+3 design.
Dose-expansion stage: participants were enrolled and treated Q3W at the dose level(s) selected from dose escalation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open-label first-in-human trial with a dose-escalation stage (classical 3+3 design; 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mg/kg Q3W; ) followed by a dose-expansion stage at the dose level(s) selected from escalation.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose-escalation six doses levels have been selected for evaluation | Experimental | Drug: SMP-656 InjectionSMP-656 administered intravenously once every 3 weeks (Q3W) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Voluntarily participate in this clinical trial, understand and comply with study procedures, and provide written informed consent voluntarily.
- Male or female; aged >= 18 years at the time of signing the informed consent form.
- Expected survival >= 12 weeks.
- Histologically or cytologically confirmed HER2-expressing or HER2-mutated advanced solid tumors .
- In the dose-expansion stage, patients must additionally meet the requirements of one of the following cohorts: (1) HER2-positive or HER2-low breast cancer; (2) HER2-mutated or -amplified NSCLC ; (3) Other HER2-positive or HER2-mutated solid tumors.
Key exclusion criteria (17 listed)
- Insufficient washout of prior antitumor therapy before the first dose: chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives (whichever is shorter); antibody therapy within 3 weeks; hormonal therapy within 2 weeks; antitumor Chinese patent medicine within 2 weeks; palliative radiotherapy within 2 weeks; radical radiotherapy within 4 weeks; nitrosoureas or mitomycin within 6 weeks; major surgery within 28 days; any other investigational antitumor agent within 28 days.
- Have received eribulin or an eribulin-containing ADC in prior lines of therapy.
- Known history of severe hypersensitivity to inetetamab, SMP-656 or any of their excipients.
- Prior anti-tumor treatment-related toxicities (alopecia excluded) that remain at Grade > 1 or have not recovered to baseline, except adverse events deemed by the Investigator not to pose a safety risk.
- Grade >= 2 peripheral neuropathy, or prior history of Grade >= 3 neurotoxicity/peripheral neuropathy, or permanent discontinuation of previous antitumor treatment due to neurotoxicity or peripheral neuropathy.
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 |
|---|---|---|
| SMP-656 InjectionAlso: SMP-656SMP-656 was supplied as a 50 mg/vial injection for intravenous infusion and given Q3W at 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 mg/kg during dose escalation and at the selected dose level(s) during dose expansion. Treatment continues until disease progression, intolerable toxicity, voluntary withdrawal, death or trial termination. | Drug | Part 1: Dose-escalation six doses levels have been selected for evaluation |
Primary outcome
Incidence of Dose-Limiting Toxicity (DLT)
Time frame: 21 days after the first dose of SMP-656
Number and percentage of participants who experienced a protocol-defined DLT during the 21-day DLT observation period after the first SMP-656 infusion, graded according to NCI CTCAE v5.0 (hematologic, hepatic and non-hematologic/non-hepatic toxicities).
Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D)
Time frame: Through study completion, up to 27 months from first dose
The MTD and/or RP2D of SMP-656 determined from the integrated analysis of DLT, safety, pharmacokinetic and preliminary antitumor activity data across the five dose levels evaluated (0.5, 1.0, 1.5, 2.0 and 2.5 mg/kg).
9 secondary outcomes
Objective Response Rate (ORR) Assessed by Investigators
Time frame: From the date of first dose to the date of first radiological documentation of disease progression or death, whichever occurs first (up to 27 months)
Duration of Response (DOR)
Time frame: From first confirmed objective response (CR/PR) up to 27 months from first dose
Progression-Free Survival (PFS)
Time frame: From the date of first dose to the date of first radiological documentation of disease progression or death, whichever occurs first (up to 27 months)
1-Year Overall Survival Rate
Time frame: 1 year after the first dose
Area Under the Concentration Versus Time Curve (AUC) of Serum SMP-656 Following First Dose
Time frame: Post first dose up to 2 years
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum SMP-656 Following First Dose
Time frame: Post first dose up to 2 years
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum SMP-656 Following First Dose
Time frame: Post first dose up to 2 years
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of SerumSMP-656 Following First Dose
Time frame: Post first dose up to 2 years
Overview of Treatment-emergent Adverse Events
Time frame: Baseline up to 28 days after the last dose of study drug
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 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. This study is not recruiting at the moment.
Jian Zhang, MD principal investigator
Fudan University
5 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 SMP-656 Injection in people with HER2-Expressing Advanced Solid Tumors and HER2-Mutated Advanced Solid Tumors, run by Chengdu SciMount Pharmatech Co., Ltd. at 5 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 9 inclusion and 17 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: finished, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose-Limiting Toxicity (DLT) (time frame: 21 days after the first dose of SMP-656). 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 6 Nov 2026.