Vudalimab for the Treatment of Locally Advanced or Metastatic Anaplastic Thyroid Cancer or Hurthle Cell Thyroid Cancer

NCT05453799 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 21N05NCI-2022-04953STU00216441P30CA060553
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests whether vudalimab works to shrink tumors in patients with anaplastic thyroid cancer or hurthle cell thyroid cancer that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as vudalimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Locally Advanced Thyroid Gland Anaplastic Carcinoma; Metastatic Thyroid Gland Anaplastic Carcinoma; Metastatic Thyroid Gland Oncocytic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Defined as the proportion of treated subjects in the Main Cohort (ATC) who experience an objective response. Objective response is defined as achieving a confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Confirmation of response should be conducted via imaging \>= 28 days after the response was first documented. The date of first response for either CR or PR will be used for the calculation of ORR.

  Up to 5 years

Secondary Outcomes (7)

• Progression-free survival (PFS)

  Up to 5 years

• PFS-16

  At 16 weeks

• Overall survival (OS)

  Up to 5 years

• Clinical benefit rate

  Up to 5 years

• Duration of response

  Up to 5 years

Study Arms (1)

Treatment (vudalimab)

EXPERIMENTAL

Patients receive vudalimab IV over 1 hour on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Vudalimab

Interventions

Vudalimab DRUG

Given IV

Also known as: Anti-PD-1/Anti-CTLA-4 XmAb20717, Anti-PD1/CTLA4 Bispecific Antibody XmAb20717, PD-1 x CTLA-4 Bispecific Antibody XmAb20717, PD-1 x CTLA-4 Dual Checkpoint Inhibitor XmAb20717, XmAb 20717, XmAb20717

Treatment (vudalimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MAIN COHORT (ANAPLASTIC THYROID CANCER \[ATC\]): Subjects enrolling in the Main Cohort must have a histologically confirmed diagnosis of anaplastic thyroid cancer (ATC). This includes cases with pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma. Diagnosis may include terminology consistent with or suggestive of: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; or poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present. (This study will not conduct central pathology review. Documentation on a standard pathology report is sufficient for determination of eligibility.)
• MAIN COHORT (ATC): Subject's anaplastic thyroid cancer (ATC) must be either 1) metastatic ATC, or 2) incurable, locally-advanced ATC
• MAIN COHORT (ATC): Subjects whose ATC carries a known BRAF V600E mutation must previously have received and failed, or be intolerant to, a BRAF/MEK inhibitor (e.g., dabrafenib or trametinib). Note: BRAF V600E mutation is not required to enroll in the trial, but if known to be present, this criterion must be met
• EXPLORATORY COHORT HURTHLE CELL THYROID CANCER \[HCC\]): Subjects enrolling in the Exploratory Cohort must have a histologically confirmed diagnosis of Hurthle cell thyroid cancer (HCC). (This study will not conduct central pathology review. Documentation on the pathology report is sufficient for determination of eligibility.)
• EXPLORATORY COHORT (HCC): Subject's Hurthle cell thyroid cancer (HCC) must be incurable, metastatic HCC
• EXPLORATORY COHORT (HCC): Subjects with HCC must previously have received and failed, or be intolerant to, at least one line of primarily anti-VEGFR tyrosine kinase inhibitor therapy (e.g., lenvatinib)
• EXPLORATORY COHORT (HCC): Subjects with HCC must have demonstrated radiographic disease progression within =\< 14 months prior to enrollment
• Subject's cancer must have progressed after treatment with all potentially curative standard therapies, or there must be no appropriate therapies available
• Subjects must have measurable disease, as assessed by RECIST 1.1
• Subjects must be \>= 18 years of age
• Subjects must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 or a Karnofsky performance status of \>= 60%
• Tissue requirements for participation in correlative studies:
• Prior to enrolling in the study, it must be determined if the subject has available adequate archival formalin-fixed paraffin embedded (FFPE) block(s)/slides containing tumor for correlative studies
• If adequate archival tissue is available, collection of the tissue for use in correlative studies is mandatory. (Documentation of sufficient archival tissue availability should be noted in the study record prior to enrollment. Archival tissue need not be submitted until after the subject has been fully registered to the study. or
• If adequate archival tissue is not available, subjects may still participate in the study. (Documentation of insufficient archival tissue availability should be noted in the study record.) In these cases, a pre-treatment fresh biopsy may be conducted per treating investigator discretion, if indicated; a portion of such biopsy tissue may be submitted for use in correlative studies, if sufficient biopsy material is available

You may not qualify if:

• Subjects must not have a known history of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to XmAb20717 or any of its excipients
• Subjects must not have previously received XmAb20717
• Subjects must not have received prior CTLA4 antibody or PD-1/PD-L1 therapy
• Washout from prohibited anti-cancer therapy: Subjects must not currently be receiving anticancer therapy (e.g., chemotherapy, radiation therapy, targeted therapy, investigational anticancer agents, immunotherapy, hormonal therapy, biologics, anti-cancer radionucleotides, other systemic anticancer agents, etc.)
• For subjects with HCC, all anticancer therapies (with the exception of surgery) must be discontinued at least 2 weeks prior to the initiation of trial therapy
• For subjects with ATC, all anticancer therapies (with the exception of surgery) must be discontinued at least 1 week prior to the initiation of trial therapy
• Notes: There is no required washout from prior surgical procedures. Due to the aggressive nature of ATC, wherein the disease progresses extremely rapidly, a 2-week washout from prior anticancer therapy is not indicated for this patient population. A 1-week washout is selected for ATC (due to it being aggressive), while a 2-week washout is selected for HCC (due to it being less aggressive)
• Washout from prohibited concomitant medication: Subjects must not have any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medication. Corticosteroids, prednisone equivalents, and other immunosuppressive medications must be discontinued within 14 days prior to first dose of trial therapy (except that inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted)
• Washout from prohibited concomitant vaccine: Subjects must not have received a live-virus vaccine within 30 days prior to the first dose of trial therapy. Subjects must not have received any other vaccine within 24 hours prior to the first dose of trial therapy. Note that while the majority of seasonal influenza vaccines (e.g., intramuscular route) do not contain live virus, the intranasal Flu-Mist is considered a live attenuated vaccine.
• Subjects must not have a known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously adequately treated brain metastases may participate, provided they are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial therapy
• Subjects must not have a known or suspected active autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and non-steroidal anti-inflammatory drugs; or celiac disease that, in the opinion of the investigator, is clinically-controlled)
• Subjects must not have received an organ allograft
• Female subjects must not be pregnant or intending to conceive from the time of informed consent through 8 months after the last dose of trial treatment. (These subjects are excluded because there is an unknown but potential risk for adverse events to the developing fetus)
• It is unknown whether XmAb20717 is excreted in human milk. Since many drugs are excreted in human milk, and due to the potential for serious adverse reactions in the nursing infant, women who are breastfeeding are not eligible for enrollment
• Subjects must not have evidence of any serious bacterial (including tuberculosis), viral (including severe acute respiratory syndrome coronavirus 2 \[SARS CoV-2\] and influenza), parasitic, or systemic fungal infections within the 30 days prior to the first dose of trial therapy

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Jochen H Lorch, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 12, 2022
• Study Start: July 21, 2022
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Locations

US (2)