MRG003 plus pucotenlimab for EGFR-positive advanced anaplastic or poorly differentiated thyroid cancer

A Phase II Clinical Trial Evaluating the Efficacy and Safety of MRG003 in Combination With Pucotenlimab for the Treatment of EGFR-positive Unresectable Locally Advanced or Metastatic ATC/PDTC

This trial will see if combining MRG003 and pucotenlimab can help adults with EGFR-positive unresectable or metastatic anaplastic or poorly differentiated thyroid cancer by shrinking tumors or slowing their growth.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: pucotenlimab, immunotherapy, radiation, prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07235566 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase II trial at Fudan University Shanghai Cancer Center testing the combination of MRG003 (an EGFR-directed antibody–drug conjugate) and pucotenlimab (a PD-1 inhibitor) in patients with EGFR-positive unresectable recurrent or metastatic anaplastic (ATC) or poorly differentiated thyroid cancer (PDTC). Patients are assigned to two cohorts based on BRAF V600E mutation status (wild-type versus mutant), with approximately 30 evaluable subjects planned per cohort. All participants receive MRG003 2.0 mg/kg plus pucotenlimab 200 mg every three weeks until disease progression or other protocol-defined discontinuation. The trial will monitor tumor response and safety to determine the activity and tolerability of the combination.

Who should consider this trial

Good fit: Adults (≥18 years) with pathologically confirmed EGFR-positive (>10% IHC) unresectable recurrent or metastatic ATC or PDTC who can provide tumor tissue, have an expected survival of ≥12 weeks, and may be treatment-naive or previously treated with targeted therapy ± immunotherapy are eligible.

Not a fit: Patients whose tumors lack EGFR expression, who are candidates for curative surgery, who have a very limited life expectancy, or who have contraindications to ADCs or PD-1 inhibitors are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, the combination could shrink tumors or slow disease progression in EGFR-positive advanced ATC/PDTC and offer a new option for a cancer with limited effective treatments.

How similar studies have performed: Combining antibody–drug conjugates with PD-1 inhibitors has shown promising signals in some other solid tumors, but this specific EGFR-ADC plus PD-1 approach remains largely untested in ATC/PDTC.

Eligibility criteria

Inclusion Criteria:

* Voluntarily sign the informed consent form and comply with the protocol requirements.
* Age ≥18 years on the day of signing the informed consent form, regardless of gender.
* Expected survival time ≥12 weeks.
* Patients with pathologically confirmed EGFR-positive ATC or PDTC, currently in a recurrent or metastatic stage and not eligible for curative resection. ATC/PDTC may coexist with differentiated thyroid cancer. EGFR positivity is defined as \>10% of tumor cells showing positive immunohistochemical staining.
* For subjects with either BRAF V600E wild-type or mutant-type, treatment-naive patients or those who have previously received targeted therapy ± immunotherapy are eligible for enrollment. Regarding neoadjuvant/adjuvant therapy, if recurrence occurs within 6 months after completing neoadjuvant/adjuvant therapy, such treatment will be considered as systemic therapy for the recurrent/metastatic stage.
* Subjects must be able to provide tumor tissue specimens (paraffin blocks, paraffin-embedded sections, or fresh tissue sections) from primary or metastatic sites for pathological testing. The most recent archived tumor tissue specimen should be used. If archived tissue is unavailable, a new biopsy must be performed.
* There must be radiographic evidence of disease progression during or after the most recent treatment, confirmed by the investigator. According to RECIST 1.1 criteria, there must be at least one measurable extracranial lesion at baseline. Measurable lesions should not have been irradiated, unless the lesion within a prior radiation field or after local treatment has demonstrated progression.
* Adverse events related to prior anti-tumor treatment have recovered to ≤ Grade 1 according to NCI CTCAE v5.0 (except for alopecia, non-clinically significant or asymptomatic laboratory abnormalities).
* ECOG performance status of 0 or 1 within 7 days prior to treatment.
* No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to treatment.
* Organ function levels must meet the following requirements within 7 days prior to treatment.
* Fertile male and female subjects of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose of the study drug. Women of childbearing potential include premenopausal women and women within 2 years of menopause. A negative serum pregnancy test result within ≤7 days prior to the first dose of the study drug is required for women of childbearing potential.

Exclusion Criteria:

* Medullary thyroid carcinoma or other malignancies not originating from thyroid follicular cells;
* History of other primary malignancies; Except for basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix; or patients who have received radical treatment and have had no recurrence within 5 years may participate in this trial;
* Received any of the following treatments:

  1. Prior treatment with an ADC drug;
  2. Treatment with an investigational drug from another clinical trial within 28 days prior to the first dose (excluding already marketed drugs);
  3. Treatment with anti-tumor Chinese patent medicines or herbal medicines within 14 days prior to the first dose;
  4. Radiotherapy within 28 days prior to the first dose, or palliative radiotherapy for bone metastases within 2 weeks prior to the first dose;
  5. Major surgery within 28 days prior to the first dose without full recovery, or planned major surgery within the first 12 weeks after receiving the study drug.
* Untreated or unstable brain parenchymal metastases, spinal cord metastases or compression, carcinomatous meningitis, or leptomeningeal metastases; Note: Patients who have received local brain therapy may be enrolled if brain imaging shows stability for at least 28 days prior to the first dose, with no evidence of cerebral edema and no requirement for corticosteroid therapy.
* Presence of third-space fluid that cannot be controlled by methods such as drainage (e.g., massive ascites, pleural effusion, pericardial effusion, etc.), or subjects who required drainage to control third-space fluid within 14 days prior to dosing;
* Any severe or uncontrolled systemic disease, in the investigator's judgment, including poorly controlled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg), poorly controlled diabetes, signs of active bleeding, etc.;
* Poorly controlled cardiac disease, including heart failure of NYHA class II or above, unstable angina, myocardial infarction within the past year, clinically significant supraventricular or ventricular arrhythmia requiring treatment, or long QT syndrome, such as QTcF \> 450 ms (men) or QTcF \> 470 ms (women);
* Evidence of active infection, including hepatitis B (requiring both HBsAg positivity and HBV DNA ≥2000 IU/ml, excluding hepatitis due to drugs or other causes), hepatitis C (requiring both anti-HCV antibody positivity and HCV RNA above the lower limit of detection), or human immunodeficiency virus (HIV) infection; uncontrolled active bacterial, other viral, fungal, rickettsial, or parasitic infections, unless treated and resolved prior to study drug administration;
* History of allergy to any component of pucotenlimab or MRG003 (histidine, histidine hydrochloride, sucrose, mannitol, and polysorbate 80), or history of ≥ Grade 3 allergy to macromolecular protein preparations/monoclonal antibodies;
* History of primary immunodeficiency or active autoimmune disease, currently using immunosuppressants or systemic hormonal therapy (at a dose ≥10 mg/day of prednisone or equivalent), and continuing use within 2 weeks prior to enrollment;
* Positive serum pregnancy test or lactating women who are unwilling to use adequate contraception during the study and for 6 months after the end of study drug treatment;
* Any other situation considered by the investigator as unsuitable for participation in this clinical trial.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Naisi Huang

Conditions: Thyroid Cancer