Stage IVB Oral Cavity Squamous Cell CarcinomaPhase 2NCT07844551
ImmunoADC Therapy for Induction Conversion in Patients With Stage IVB OSCC/OPSCC
A Phase 2 study testing Becotatug Vedotin (MRG003), Pucotenlimab and Cisplatin in people with Stage IVB Oral Cavity Squamous Cell Carcinoma and Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8, run by Huashan Hospital.
Trial summary
To evaluate the efficacy and safety of Becotatug Vedotin (EGFR-targeted ADC, MRG003) plus Pucotenlimab (PD-1 inhibitor), compared with platinum-based chemotherapy/chemoradiotherapy, as an induction conversion regimen for downstaging primary stage IVB oral squamous cell carcinoma or HPV16-negative oropharyngeal… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stage IVB Oral Cavity Squamous Cell Carcinoma, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
- What is being tested?
- Becotatug Vedotin (MRG003), Pucotenlimab and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 20 Oct 2026to 30 Dec 2030
- Phase
- Phase 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status: 0-1;
- Histopathologically confirmed oral/oropharyngeal squamous cell carcinoma, including tumors of the tongue, gingiva, buccal mucosa, floor of mouth, hard palate, retromolar trigone, base of tongue, soft palate, or parapharyngeal region;
- Clinical stage IVB (cT1-4N3M0 or cT4bN0-3M0, AJCC 8th edition);
- At least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
- Complete blood count: white blood cell count >3,000/mm3, hemoglobin >8 g/L, and platelet count >80,000/mm3;
- Hepatic function: alanine aminotransferase/aspartate aminotransferase (ALT/AST) <2.5 times the upper limit of normal (ULN), and bilirubin <1.5 times the ULN;
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- Renal function: serum creatinine <1.5 times the ULN;
- Positive PD-L1 expression (combined positive score [CPS] >=1) and positive EGFR expression (immunohistochemistry [IHC] 2+ or 3+);
- Written informed consent provided.
Who cannot join
- Unresolved toxicity of grade 2 or higher due to prior anticancer therapy;
- Known grade 3-4 hypersensitivity reaction to any study treatment;
- Active severe clinical infection (>grade 2 infection according to NCI-CTCAE version 5.0);
- Uncontrolled hypertension or active cardiovascular disease, including cerebrovascular accident within 6 months before randomization, myocardial infarction within 6 months before randomization, unstable angina, congestive heart failure of New York Heart Association (NYHA; Appendix 5) class II or higher, or a serious arrhythmia that cannot be controlled with medication or may potentially affect study treatment;
- Active autoimmune disease requiring systemic immunomodulatory or corticosteroid therapy for a chronic condition (e.g., disease-modifying drugs, glucocorticoids, or immunosuppressants). Replacement therapy, such as thyroxine, insulin, or physiologic glucocorticoid replacement for adrenal or pituitary insufficiency, is not considered systemic therapy;
- History of another malignancy and its treatment;
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- History of radiotherapy to the maxillofacial and neck region;
- HPV-positive oropharyngeal cancer;
- Pregnant or breastfeeding women;
- Known history of human immunodeficiency virus (HIV) infection, or uncontrolled active hepatitis B, defined as hepatitis B surface antigen (HBsAg) positivity together with a detectable hepatitis B virus DNA (HBV-DNA) copy number above the upper limit of normal of the local laboratory at the study center;
- Participation in another clinical study within 30 days before enrollment;
- Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Immunotherapy Combined With ADC (MRG003) for Induction Conversion Therapy to Downstage Primary Stage IVB Oral/Oropharyngeal Squamous Cell Carcinoma：An Exploratory Two-Arm Randomized Controlled Trial (Transforming Trial)
To evaluate the efficacy and safety of Becotatug Vedotin (EGFR-targeted ADC, MRG003) plus Pucotenlimab (PD-1 inhibitor), compared with platinum-based chemotherapy/chemoradiotherapy, as an induction conversion regimen for downstaging primary stage IVB oral squamous cell carcinoma or HPV16-negative oropharyngeal squamous cell carcinoma.
Read the detailed description
More than 60% of patients with head and neck squamous cell carcinoma (HNSCC) have locally advanced disease at initial diagnosis, often presenting with a large primary tumor accompanied by marked local invasion and/or regional lymph-node metastasis. In patients with clinical stage IVB oral squamous cell carcinoma (OSCC), tumors frequently invade the masticator space, pterygoid plates, or skull base and/or encase the internal carotid artery; and in patients with clinical stage IVB oropharyngeal squamous cell carcinoma (OPSCC), tumors frequently invade the lateral pterygoid muscle, pterygoid plates, lateral nasopharyngeal wall, or skull base, or encase the carotid artery. Because of extensive infiltration and involvement of critical anatomical structures, radical surgery faces two major challenges in this population: firstly, R0 resection is difficult to achieve, resulting in rapid postoperative recurrence; secondly, radical surgery inevitably causes disfiguring tissue defects and severe functional loss, leading to extremely poor quality of life. The 1- to 2-year overall survival rate for these patients ranges from 22% to 35%.
For the patients with unresectable primary stage IVB OSCC or human papillomavirus (HPV)-negative OPSCC, current standard treatment consists of platinum-based concurrent chemoradiotherapy or radiotherapy following platinum-based induction chemotherapy. Although these regimens are widely used, their efficacy remains unsatisfactory. In recent years, additional approaches have been developed and evaluated, including monoclonal antibodies targeting epidermal growth factor receptor (EGFR), novel radiotherapy fractionation schedules, and induction or neoadjuvant chemotherapy regimens; however, none has demonstrated a clear improvement over standard concurrent chemoradiotherapy. Standard concurrent chemoradiotherapy may also cause toxicities such as late-onset dysphagia and severe xerostomia. Accordingly, developing new therapeutic strategies to improve outcomes in this population has become a major focus in the field of HNSCC.
Neoadjuvant therapy refers to antitumor treatment administered before surgery with the aims of reducing tumor volume, increasing the likelihood of surgical resection, and decreasing the risk of postoperative recurrence; it may therefore improve outcomes in locally advanced malignancies. Given the close interaction between antibody-drug conjugate (ADC) and the host immune system, the combination of these two modalities may theoretically produce synergistic antitumor effects and improve treatment outcomes. Therefore, this prospective, exploratory, two-arm, randomized controlled clinical trial will compare becotatug vedotin, an EGFR-targeted ADC, plus pucotenlimab, an anti-PD-1 monoclonal antibody, with current standard therapy consisting of platinum-based induction chemotherapy or chemoradiotherapy. The investigational regimen is expected to induce deep tumor regression in patients with unresectable primary stage IVB OSCC/OPSCC, achieve tumor downstaging, convert unresectable lesions into lesions amenable to R0 resection, and allow evaluation of efficacy and safety, including potential survival benefits. The study may provide a new therapeutic strategy for patients with stage IVB HNSCC.
- Conditions
- Stage IVB Oral Cavity Squamous Cell Carcinoma, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
- Being tested
- Becotatug Vedotin (MRG003), Pucotenlimab, Cisplatin
- Keywords
- Combination of immunotherapy and antibody-drug conjugate, Stage IVB OSCC or OPSCC, Induction conversion
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Becotatug Vedotin (MRG003)Drug
2.3 mg/kg by intravenous infusion once every 21 days
PucotenlimabDrug
200 mg by intravenous infusion once every 21 days
CisplatinDrug
75mg/m2 by intravenous infusion once every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Combination therapy of immunotherapy and antibody-drug conjugate. Drugs: Becotatug vedotin: 2.3 mg/kg by intravenous infusion once every 21 days. Pucotenlimab: 200 mg by intravenous infusion once every 21 days.
Each treatment cycle is 21 days, and two cycles will be administered. On each dosing day, pucotenlimab will be infused first, followed by becotatug vedotin. Receives: Drug: Becotatug Vedotin (MRG003); Drug: Pucotenlimab |
| Control Arm | Active comparator | Participants in the control arm will undergo MDT assessment by the investigators and receive a platinum-based induction chemotherapy regimen. Cisplatin: 75mg/m2 by intravenous infusion once every 21 days. Each treatment cycle is 21 days, and two cycles will be administered. All required assessments must be completed within 3 days before dosing. Treatment may continue only after the safety evaluation is satisfactory. Receives: Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical downstaging rate
The ratio of patients could achieve clinical downstaging after two cycles of drug treatment according to the AJCC 8th edition.
Measured: 6 months
Secondary outcomes (3)
Surgical R0 resection rate
The ratio of R0 resection, complete removal of all grossly visible tumor with no residual tumor cells at the microscopic resection margins, i.e., microscopically negative margins.
Measured: 6 months
Rate of 2-year overall survival
Overall survival is calculated from the date of randomization to death. The rate of 2-year overall survival is reported as the percentage of patients who are overall survival for 2 years from the date of randomization.
Measured: 2 years
Rate of 2-year progression free survival
Progression free survival is calculated from the date of randomization to local tumor recurrence or progression, locoregional recurrence or progression, distant metastasis, or death. The rate of 2-year progression free survival is reported as the percentage of patients who are progression free survival for 2 years from the date of randomization.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2026
- Study start20 Oct 2026 (estimated)
- Primary completion30 Oct 2028 (estimated)
- Study completion30 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IVB Oral Cavity Squamous Cell CarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lai-ping Zhong, Huashan Hospital
- Investigators
- Lai-ping Zhong, Principal investigator, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07844551
- Sponsor's protocol ID
- Transforming
- Status last verified
- Sep 2026
- First submitted
- 22 Sep 2026
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the completion of the trial.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy Combined With ADC (MRG003) for Induction Conversion Therapy to Downstage Primary Stage IVB Oral/Oropharyngeal Squamous Cell Carcinoma：An Exploratory Two-Arm Randomized Controlled Trial (Transforming Trial)
- ClinicalTrials.gov ID
- NCT07844551
- Acronym / sponsor ID
- Transforming
- Conditions
- Stage IVB Oral Cavity Squamous Cell Carcinoma, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
- Keywords
- Combination of immunotherapy and antibody-drug conjugate, Stage IVB OSCC or OPSCC, Induction conversion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 20 Oct 2026 (estimated)
- Primary completion
- 30 Oct 2028 (estimated)
- Study completion
- 30 Dec 2030 (estimated)
- First posted
- 28 Sep 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.
To evaluate the efficacy and safety of Becotatug Vedotin (EGFR-targeted ADC, MRG003) plus Pucotenlimab (PD-1 inhibitor), compared with platinum-based chemotherapy/chemoradiotherapy, as an induction conversion regimen for downstaging primary stage IVB oral squamous cell carcinoma or HPV16-negative oropharyngeal squamous cell carcinoma.
Detailed description
More than 60% of patients with head and neck squamous cell carcinoma (HNSCC) have locally advanced disease at initial diagnosis, often presenting with a large primary tumor accompanied by marked local invasion and/or regional lymph-node metastasis. In patients with clinical stage IVB oral squamous cell carcinoma (OSCC), tumors frequently invade the masticator space, pterygoid plates, or skull base and/or encase the internal carotid artery; and in patients with clinical stage IVB oropharyngeal squamous cell carcinoma (OPSCC), tumors frequently invade the lateral pterygoid muscle, pterygoid plates, lateral nasopharyngeal wall, or skull base, or encase the carotid artery. Because of extensive infiltration and involvement of critical anatomical structures, radical surgery faces two major challenges in this population: firstly, R0 resection is difficult to achieve, resulting in rapid postoperative recurrence; secondly, radical surgery inevitably causes disfiguring tissue defects and severe functional loss, leading to extremely poor quality of life. The 1- to 2-year overall survival rate for these patients ranges from 22% to 35%.
For the patients with unresectable primary stage IVB OSCC or human papillomavirus (HPV)-negative OPSCC, current standard treatment consists of platinum-based concurrent chemoradiotherapy or radiotherapy following platinum-based induction chemotherapy. Although these regimens are widely used, their efficacy remains unsatisfactory. In recent years, additional approaches have been developed and evaluated, including monoclonal antibodies targeting epidermal growth factor receptor (EGFR), novel radiotherapy fractionation schedules, and induction or neoadjuvant chemotherapy regimens; however, none has demonstrated a clear improvement over standard concurrent chemoradiotherapy. Standard concurrent chemoradiotherapy may also cause toxicities such as late-onset dysphagia and severe xerostomia. Accordingly, developing new therapeutic strategies to improve outcomes in this population has become a major focus in the field of HNSCC.
Neoadjuvant therapy refers to antitumor treatment administered before surgery with the aims of reducing tumor volume, increasing the likelihood of surgical resection, and decreasing the risk of postoperative recurrence; it may therefore improve outcomes in locally advanced malignancies. Given the close interaction between antibody-drug conjugate (ADC) and the host immune system, the combination of these two modalities may theoretically produce synergistic antitumor effects and improve treatment outcomes. Therefore, this prospective, exploratory, two-arm, randomized controlled clinical trial will compare becotatug vedotin, an EGFR-targeted ADC, plus pucotenlimab, an anti-PD-1 monoclonal antibody, with current standard therapy consisting of platinum-based induction chemotherapy or chemoradiotherapy. The investigational regimen is expected to induce deep tumor regression in patients with unresectable primary stage IVB OSCC/OPSCC, achieve tumor downstaging, convert unresectable lesions into lesions amenable to R0 resection, and allow evaluation of efficacy and safety, including potential survival benefits. The study may provide a new therapeutic strategy for patients with stage IVB HNSCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Becotatug Vedotin (MRG003), Drug: PucotenlimabCombination therapy of immunotherapy and antibody-drug conjugate. Drugs: Becotatug vedotin: 2.3 mg/kg by intravenous infusion once every 21 days. Pucotenlimab: 200 mg by intravenous infusion once every 21 days. Each treatment cycle is 21 days, and two cycles will be administered. On each dosing day, pucotenlimab will be infused first, followed by becotatug vedotin. |
| Control Arm | Active comparator | Drug: CisplatinParticipants in the control arm will undergo MDT assessment by the investigators and receive a platinum-based induction chemotherapy regimen. Cisplatin: 75mg/m2 by intravenous infusion once every 21 days. Each treatment cycle is 21 days, and two cycles will be administered. All required assessments must be completed within 3 days before dosing. Treatment may continue only after the safety evaluation is satisfactory. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status: 0-1;
- Histopathologically confirmed oral/oropharyngeal squamous cell carcinoma, including tumors of the tongue, gingiva, buccal mucosa, floor of mouth, hard palate, retromolar trigone, base of tongue, soft palate, or parapharyngeal region;
- Clinical stage IVB (cT1-4N3M0 or cT4bN0-3M0, AJCC 8th edition);
- At least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
- Complete blood count: white blood cell count >3,000/mm3, hemoglobin >8 g/L, and platelet count >80,000/mm3;
Key exclusion criteria (12 listed)
- Unresolved toxicity of grade 2 or higher due to prior anticancer therapy;
- Known grade 3-4 hypersensitivity reaction to any study treatment;
- Active severe clinical infection (>grade 2 infection according to NCI-CTCAE version 5.0);
- Uncontrolled hypertension or active cardiovascular disease, including cerebrovascular accident within 6 months before randomization, myocardial infarction within 6 months before randomization, unstable angina, congestive heart failure of New York Heart Association (NYHA; Appendix 5) class II or higher, or a serious arrhythmia that cannot be controlled with medication or may potentially affect study treatment;
- Active autoimmune disease requiring systemic immunomodulatory or corticosteroid therapy for a chronic condition (e.g., disease-modifying drugs, glucocorticoids, or immunosuppressants). Replacement therapy, such as thyroxine, insulin, or physiologic glucocorticoid replacement for adrenal or pituitary insufficiency, is not considered systemic therapy;
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 |
|---|---|---|
| Becotatug Vedotin (MRG003)2.3 mg/kg by intravenous infusion once every 21 days | Drug | Experimental Arm |
| Pucotenlimab200 mg by intravenous infusion once every 21 days | Drug | Experimental Arm |
| Cisplatin75mg/m2 by intravenous infusion once every 21 days | Drug | Control Arm |
Primary outcome
Clinical downstaging rate
Time frame: 6 months
The ratio of patients could achieve clinical downstaging after two cycles of drug treatment according to the AJCC 8th edition.
3 secondary outcomes
Surgical R0 resection rate
Time frame: 6 months
Rate of 2-year overall survival
Time frame: 2 years
Rate of 2-year progression free survival
Time frame: 2 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 28 Sep 2026.
- Individual participant dataSharing planned: Yes. After the completion of the trial.
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Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer
Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
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.
Lai-ping Zhong principal investigator
Huashan Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Becotatug Vedotin (MRG003), Pucotenlimab and Cisplatin in people with Stage IVB Oral Cavity Squamous Cell Carcinoma and Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8, run by Huashan Hospital.
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 12 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: opening soon, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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 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 Lai-ping Zhong, MD, PhD (+862152888915, zhonglp@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical downstaging rate (time frame: 6 months). 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 28 Sep 2026.