Squamous Cell CarcinomaPhase 2TRIFECTA-SCCNCT07896811
Triplet Immunotherapy For Exhausted Cell Targets in Advanced Squamous Cell Carcinoma
A Phase 2 study testing Induction radiotherapy, Vilastobart and Opdualag in people with Squamous Cell Carcinoma, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
The investigators propose a phase II signal-finding study, TRIFECTA-SCC, to determine whether four 100 mg IV every 6 week doses of vilastobart plus six every 4 week doses of Opdualag with induction radiotherapy can lead to ≥50% 6-month progression-free survival for patients with recurrent and/or metastatic squamous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma
- What is being tested?
- Induction radiotherapy, Vilastobart and Opdualag
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2027to 1 Feb 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years or older with pathology-confirmed recurrent and/or metastatic (R/M) squamous cell carcinoma (SCC) who have not received systemic therapy specifically for R/M SCC. Tumors reported as mixed histology are ineligible. Patients must have 1-5 R/M lesions. Contiguous matted nodal conglomerates will be counted as a single lesion.
- Initial primary site of disease is not restricted and may include the head and neck, lung, skin, urogenital, gynecological, anal canal, gastrointestinal, or squamous cell carcinoma of an unknown primary site.
- Patients must have measurable disease under RECIST v1.1. A superficial lesion may be measured with calipers if it meets RECIST clinical measurability requirements and is documented reproducibly. Baseline target lesions and measurement methods must be recorded before radiotherapy.
- Patients may have recurrent disease as a single lesion or multiple metastatic deposits. If a single recurrent lesion, it must be considered unresectable by the treating oncologic surgeon, either technically or functionally (i.e., morbidity of resection outweighs potential benefit of resection).
- Any PD-L1 combined positive score (CPS).
- Disease may be human papillomavirus (HPV)-positive or HPV-negative.
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- Prior anti-PD-1 and/or anti-CTLA-4 therapy given with curative intent for the initial primary cancer, including neoadjuvant, definitive or adjuvant treatment, is permitted. Recurrence during or after such therapy is eligible without a minimum recurrence-free interval, provided no systemic therapy has been initiated specifically for R/M SCC. Patients cannot have had Grade ≥3 irAEs or an immune-mediated event for which rechallenge is contraindicated.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Obtain Thyroid-Stimulating Hormone (TSH) and free T4 at screening; repeat as specified. A thyroid abnormality alone is not exclusionary if clinically stable on appropriate management.
- Female patients must meet one of the following:
- Postmenopausal for at least one year before the screening visit, or
- Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), or
- If subject is of childbearing potential (defined as not satisfying either of the above two criteria), meet either (i) or (ii):
- Use effective contraception from consent through at least 5 months after the last Opdualag dose and at least 90 days after the last vilastobart dose, whichever ends later. Acceptable methods and pregnancy potential must be documented under institutional practice. This protocol retains a two-method approach, unless a highly effective method or qualifying abstinence is documented by the investigator.
- Agree to practice true abstinence for the full prevention interval in (i) when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post ovulation methods] and withdrawal are not acceptable contraception methods).
- Male patients, even if surgically sterilized (i.e., status post vasectomy), must meet (a) or (c), and also comply with (b) when applicable:
- Use effective barrier contraception throughout treatment and for at least 90 days after the last vilastobart dose, or longer if subsequently required by an approved protocol amendment. If the partner can become pregnant, use an additional effective method unless qualifying abstinence applies.
- Also adhere to any applicable study-specific pregnancy prevention program; this is additional to (a) or (c).
- Agree to practice true abstinence throughout treatment and for at least 90 days after the last vilastobart dose when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Ability to understand a written informed consent document, and the willingness to sign it.
Who cannot join
- Central nervous system metastasis.
- Greater than 5 metastatic deposits. Contiguous matted nodal conglomerates will be counted as a single lesion.
- Any patient with a lesion requiring acute cytoreduction through use of induction chemotherapy, as determined by the treating medical oncologist.
- Solid organ transplant or autoimmune disease requiring chronic systemic immunosuppression. Stable autoimmune disease that does not require systemic immunosuppression is permitted after PI review, with specialist input when indicated. Active autoimmune disease that makes immunotherapy unsafe is exclusionary until adequately controlled. Physiologic hormone replacement and topical or inhaled therapy alone do not constitute chronic systemic immunosuppression. Prior severe immune-related toxicity and contraindications to rechallenge remain exclusionary under Section 4.5.1 of the study protocol.
- Performance status Eastern Cooperative Oncology Group (ECOG) ≥ 3.
- A concurrent active separate metastatic malignancy of a different histology than SCC. However, any previously treated malignancy considered in remission at the time of enrollment is permitted.
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- Any of the following severe laboratory abnormalities within 14 days of registration:
- Sodium <128 mmol/L or >155 mmol/L.
- Potassium <3.0 mmol/L or >6 mmol/L.
- Glucose <40 mg/dl or >400 mg/dl.
- Total serum calcium, adjusted for albumin, <7 mg/dL or >12.5 mg/dL. These limits do not apply to ionized calcium.
- Magnesium <0.9 mg/dl or >3 mg/dl.
- estimated glomerular filtration rate (eGFR) ≤40 mL/min.
- aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≥3 x upper limit of normal (ULN).
- Total bilirubin ≥1.5 x ULN. Participants with documented Gilbert syndrome may have total bilirubin ≤3 x ULN. Assess for active hepatic disease or obstruction when clinically indicated; treatment-emergent hepatic toxicity is managed.
- Absolute Neutrophil Count (ANC) ≤1 ×10^9/L
- Platelets ≤50 ×10^9/L
- Hemoglobin (Hgb) ≤8 g/dL
- Abnormal values corrected into the acceptable range are permitted. Document qualifying repeat results within the required screening window before confirming eligibility and registration.
- Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to enrollment.
- Transmural myocardial infarction within 3 months prior to enrollment.
- Medical or psychiatric illness that would compromise treatment tolerance or study participation, including uncontrolled clinically significant infection. Defer registration until such infection is adequately controlled. Well-controlled HIV, hepatitis B or hepatitis C does not by itself exclude participation. The principal investigator must document infection control, adequate organ function and a treatment/monitoring plan, with infectious-disease or hepatology input when needed, including antiviral therapy and reactivation monitoring where indicated.
- Pregnancy, breastfeeding, or inability/unwillingness to follow the contraception requirements above. Breastfeeding is prohibited during study treatment and until at least 5 months after the last Opdualag dose and 90 days after the last vilastobart dose, whichever is later.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Medical College of Wisconsin Cancer Center Clinical Trials Office contact
United States1 site
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Phase II Study of Triplet Immunotherapy For Exhausted Cell Targets in Advanced Squamous Cell Carcinoma (TRIFECTA-SCC)
The investigators propose a phase II signal-finding study, TRIFECTA-SCC, to determine whether four 100 mg IV every 6 week doses of vilastobart plus six every 4 week doses of Opdualag with induction radiotherapy can lead to ≥50% 6-month progression-free survival for patients with recurrent and/or metastatic squamous cell carcinoma. Patients with pathology-confirmed squamous cell carcinoma, previously untreated in the recurrent and/or metastatic setting, and adequate organ function will be included.
- Conditions
- Squamous Cell Carcinoma
- Being tested
- Induction radiotherapy, Vilastobart, Opdualag
- Keywords
- squamous cell carcinoma
- Medical subject headings
- Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction radiotherapyRadiation
35 Gy in five fractions to all eligible lesions.
VilastobartDrug
Also called XTX-101
four vilastobart 100 mg IV doses every 6 weeks at Weeks 0, 6, 12, and 18
OpdualagDrug
Also called Nivolumab and relatlimab-rmbw
six Opdualag doses every 4 weeks at Weeks 0, 4, 8, 12, 16, and 20
| Study group | Role | What they receive |
|---|---|---|
| Induction radiotherapy with Immunotherapy | Experimental | Patients will receive 35 Gy in five fractions to all eligible recurrent/metastatic lesions. Post-RT immunotherapy should start within 72 hours after the final fraction. Receives: Radiation: Induction radiotherapy; Drug: Vilastobart; Drug: Opdualag |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-month Progression-Free Survival
This measure is the number of subjects without progression at six months.
Measured: Up to six calendar months and 14 days after the first radiation fraction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study start1 Feb 2027 (estimated)
- Primary completion1 Aug 2029 (estimated)
- Study completion1 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stuart Wong, Medical College of Wisconsin
- Investigators
- Stuart J Wong, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07896811
- Sponsor's protocol ID
- IIT-WONG-TRIFECTA-SCC
- Acronym
- TRIFECTA-SCC
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Triplet Immunotherapy For Exhausted Cell Targets in Advanced Squamous Cell Carcinoma (TRIFECTA-SCC)
- ClinicalTrials.gov ID
- NCT07896811
- Acronym / sponsor ID
- TRIFECTA-SCC / IIT-WONG-TRIFECTA-SCC
- Conditions
- Squamous Cell Carcinoma
- Keywords
- squamous cell carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 1 Feb 2027 (estimated)
- Primary completion
- 1 Aug 2029 (estimated)
- Study completion
- 1 Feb 2030 (estimated)
- First posted
- 27 Oct 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.
The investigators propose a phase II signal-finding study, TRIFECTA-SCC, to determine whether four 100 mg IV every 6 week doses of vilastobart plus six every 4 week doses of Opdualag with induction radiotherapy can lead to ≥50% 6-month progression-free survival for patients with recurrent and/or metastatic squamous cell carcinoma. Patients with pathology-confirmed squamous cell carcinoma, previously untreated in the recurrent and/or metastatic setting, and adequate organ function will be included.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Induction radiotherapy with Immunotherapy | Experimental | Radiation: Induction radiotherapy, Drug: Vilastobart, Drug: OpdualagPatients will receive 35 Gy in five fractions to all eligible recurrent/metastatic lesions. Post-RT immunotherapy should start within 72 hours after the final fraction. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients 18 years or older with pathology-confirmed recurrent and/or metastatic (R/M) squamous cell carcinoma (SCC) who have not received systemic therapy specifically for R/M SCC. Tumors reported as mixed histology are ineligible. Patients must have 1-5 R/M lesions. Contiguous matted nodal conglomerates will be counted as a single lesion.
- Initial primary site of disease is not restricted and may include the head and neck, lung, skin, urogenital, gynecological, anal canal, gastrointestinal, or squamous cell carcinoma of an unknown primary site.
- Patients must have measurable disease under RECIST v1.1. A superficial lesion may be measured with calipers if it meets RECIST clinical measurability requirements and is documented reproducibly. Baseline target lesions and measurement methods must be recorded before radiotherapy.
- Patients may have recurrent disease as a single lesion or multiple metastatic deposits. If a single recurrent lesion, it must be considered unresectable by the treating oncologic surgeon, either technically or functionally (i.e., morbidity of resection outweighs potential benefit of resection).
- Any PD-L1 combined positive score (CPS).
Key exclusion criteria (23 listed)
- Central nervous system metastasis.
- Greater than 5 metastatic deposits. Contiguous matted nodal conglomerates will be counted as a single lesion.
- Any patient with a lesion requiring acute cytoreduction through use of induction chemotherapy, as determined by the treating medical oncologist.
- Solid organ transplant or autoimmune disease requiring chronic systemic immunosuppression. Stable autoimmune disease that does not require systemic immunosuppression is permitted after PI review, with specialist input when indicated. Active autoimmune disease that makes immunotherapy unsafe is exclusionary until adequately controlled. Physiologic hormone replacement and topical or inhaled therapy alone do not constitute chronic systemic immunosuppression. Prior severe immune-related toxicity and contraindications to rechallenge remain exclusionary under Section 4.5.1 of the study protocol.
- Performance status Eastern Cooperative Oncology Group (ECOG) ≥ 3.
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 |
|---|---|---|
| Induction radiotherapy35 Gy in five fractions to all eligible lesions. | Radiation | Induction radiotherapy with Immunotherapy |
| VilastobartAlso: XTX-101four vilastobart 100 mg IV doses every 6 weeks at Weeks 0, 6, 12, and 18 | Drug | Induction radiotherapy with Immunotherapy |
| OpdualagAlso: Nivolumab and relatlimab-rmbwsix Opdualag doses every 4 weeks at Weeks 0, 4, 8, 12, 16, and 20 | Drug | Induction radiotherapy with Immunotherapy |
Primary outcome
Six-month Progression-Free Survival
Time frame: Up to six calendar months and 14 days after the first radiation fraction
This measure is the number of subjects without progression at six months.
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 27 Oct 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.
Medical College of Wisconsin Cancer Center Clinical Trials Office contact
Stuart J Wong, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Induction radiotherapy, Vilastobart and Opdualag in people with Squamous Cell Carcinoma, run by Medical College of Wisconsin at 1 site in United States.
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 20 inclusion and 23 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 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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 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 Medical College of Wisconsin Cancer Center Clinical Trials Office (866-680-0505 ext. 8900, cccto@mcw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six-month Progression-Free Survival (time frame: Up to six calendar months and 14 days after the first radiation fraction). 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 27 Oct 2026.