Vaginal Squamous Cell CarcinomaPhase 2ARCANANCT07804966
Sac-TMT in Vaginal and Vulvar Cancers
A Phase 2 study testing Sacituzumab Tirumotecan (sac-TMT) in people with Vaginal Squamous Cell Carcinoma and Vulvar Squamous Cell Carcinoma, run by Latin American Cooperative Oncology Group at 12 sites in Brazil.
Trial summary
The ARCANA trial (LACOG 1724) is a single-arm, non-randomized, multi-center, parallel, two-cohort Phase II clinical study designed to evaluate the efficacy and safety of sacituzumab tirumotecan (sac-TMT, MK-2870) as a second-line or subsequent treatment in patients with advanced or metastatic vaginal and vulvar… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Vaginal Squamous Cell Carcinoma, Vulvar Squamous Cell Carcinoma
- What is being tested?
- Sacituzumab Tirumotecan (sac-TMT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 12 sitesBrazil
- Study dates
- Jan 2027to Jan 2032
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a histologically- or cytologically confirmed diagnosis of squamous cell carcinoma of vagina (cohort A) or vulvar (cohort B) origin
- Advanced disease, defined as presence of metastatic disease or locally advanced disease not amenable to curative therapy in the opinion of the investigator
- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions.
- Has received up to 2 prior lines of systemic therapy. Disease progression to first-line or second-line platinum-based chemotherapy for locally advanced/metastatic disease. Previous anti-PD-1/anti-PD-L1 therapy is allowed. Disease progression within 6 months of (neo) adjuvant chemotherapy completion is considered first-line of therapy. The participant may have received prior radiation with or without radio-sensitizing chemotherapy at least >2 weeks before the start of study treatment.
- At least 18 years of age at the time of providing informed consent.
- A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
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- Is not a POCBP OR
- Is a POCBP and: - Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 4 during the intervention period and for at least the time needed to eliminate the study intervention after the last dose of study intervention. The participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for the study intervention is 210 days. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
- Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.4.5.
- Abstains from breastfeeding during the study intervention period and for at least 10 days after study intervention.
- Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
- 8. Has provided an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion from any site not previously irradiated. Sites should follow local guidelines regarding fresh tissue collection. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slide. Newly obtained biopsies are preferred to archived tissue (recommended 22-28 slides). 9. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible.
- 10. Adequate organ function as defined in the following table (Table 2). Specimens must be collected within 14 days before the start of study intervention.
- 11. Has ECOG performance status of 0 or 1. 12. Be willing and able to comply with study procedures, laboratory tests, and other requirements of the study.
- 13. HIV testing at screening is not required unless there is a known history of HIV infection. HIV-infected participants must have well-controlled HIV on ART, defined as:
- Having a CD4+ T-cell count ≥350 cells/mm3 at the time of screening
- Having achieved and maintained virologic suppression, defined as confirmed HIV RNA level below 50 or the LLOQ using the locally available assay, at the time of screening and for at least 12 weeks before screening
- Absence of any AIDS-defining opportunistic infections within the past 12 months
- Being on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before enrollment and agreeing to continue ART throughout the study Note: The ART regimen must not contain any antiretroviral medications that are strong CYP3A4 inducers/inhibitors/substrates. Refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally-approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor/substrate of CYP3A4.
- 14. Hepatitis B testing at screening is not required unless there is a known history of HBV infection. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before enrollment.
- Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
- 15. Hepatitis C testing at screening is not required unless there is a known history of HCV infection. Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
- Note: Participants must have completed curative antiviral therapy at least 4 weeks before enrollment.
Who cannot join
- Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention. Prior/Concomitant Therapy
- Received prior treatment with a TROP2-targeted ADC.
- Received prior treatment with a topoisomerase 1 inhibitor-containing ADC.
- Received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention.
- Received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has had radiation pneumonitis.
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- Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
- Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- Refer to Section 6.2 for information on COVID-19 vaccines.
- Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks.
- Note: A list of strong inducers/inhibitors of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally-approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor of CYP3A4. Prior/Concurrent Clinical Study Experience
- Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.
- Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. Diagnostic Assessments
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (excluding carcinoma in situ of the bladder) who have undergone potentially curative resection are not excluded.
- History of CNS metastases and/or carcinomatous meningitis.
- Has an active infection requiring systemic therapy within 4 weeks prior to the first dose of study treatment except those permitted as outlined in Section 5.1.
- Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual's ability to cooperate with the requirements of the study, or interfere with the individual's participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator.
- Other Exclusions
- Severe hypersensitivity (Grades ≥3) to study intervention, any of their excipients, and/or to another biologic therapy.
- Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary.
- Note: Participants who underwent major surgery must have adequately recovered from toxicity and/or complications from the surgery before starting study intervention.
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Brazil12 sites
Hospital Ophir Loyola
Belém, Pará, 66063-240
Cynthia Lins Pereira, +5591981298434, cpchol@ophirloyola.pa.gov.br
Marcella Coelho Mesquita Fernandes
UFMG - Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, 30130-100
Carla de Oliveira do Nascimento, +553133079255, carla-nascimento.cn@ebserh.gov.br
Angélica Nogueira Rodrigues
Pronutrir - Suporte Nutricional e Quimioterapia
Fortaleza, Ceará, 60810-180
Antonia Felizalvina Barroso Dias, +5585992656791, branca.dias@pronutrir.com.br
Rosane Oliveira de Sant'Ana
Hospital Napoleão Laureano
João Pessoa, Paraíba, 58013-140
Débora Alves Rodrigues de Lima, +5583988250322, debora.enf.hnl@gmail.com
Thiago Lins da Costa Almeida
Liga Norte Riograndense Contra o Câncer
Natal, Rio Grande do Norte, 59062-000
Ana Paula Ferreira Costa, +558440095595, anapaula.costa@liga.org.br
Sulene Cunha Sousa Oliveira
Futtura Oncologia - Hub de Pesquisa Clínica
Porto Alegre, Rio Grande do Sul, 90470-340
Tereza Mandarino, 555199905582, tereza.mandarino@futturaoncologia.com
Fernanda Cano Casarotto
INCA - Instituto Nacional de Câncer
Rio de Janeiro, Rio de Janeiro, 20230-130
Flavia Vieira Guerra Alves, +5521981127437, falves@inca.gov.br
Andreia Cristina de Melo
Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel (Oncoclínicas)
Salvador, Estado de Bahia, 40050-410
Nivana Borges do Sacramento, +557122038476, nivana.sacramento@santacasaba.org.br
Daniela Galvão Barros de Oliveira
FUNFARME - Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José do Rio Preto, São Paul, 15090-000
Kátia Nishiyama, +551732011771, katia.nishiyama@centrodepesquisacip.com.br
Camila Gardin Ferrari
HIAE - Hospital Israelita Albert Einstein
São Paulo, HIAE - Hospital Israelita Albert Einstein, 05653-000
Fernando Cotait Maluf, +5511981214499, maluffc@uol.com.br
ICESP - Instituto do Câncer do Estado de São Paulo
São Paulo, São Paulo, 01246-000
Marlene Salgado Fidelis, +551138932645, marlene.salgado@hc.fm.usp.br
Maria Del Pilar Estevez Diz
Centro de Pesquisa Vencer e Oncoclínica
Teresina, Piauí, 60449-200
Fernanda Bitencourt da Rocha, +5586994370620, VENCERPESQUISACLINICA@GMAIL.COM
Danilo da Fonseca Reis Silva
About this study
Official title: A Single-arm Phase II Trial of Sacituzumab Tirumotecan (Sac-TMT) as Second-line Treatment for Advanced/Metastatic Vaginal and Vulvar Squamous Cell Carcinoma - ARCANA Trial (LACOG 1724)
The ARCANA trial (LACOG 1724) is a single-arm, non-randomized, multi-center, parallel, two-cohort Phase II clinical study designed to evaluate the efficacy and safety of sacituzumab tirumotecan (sac-TMT, MK-2870) as a second-line or subsequent treatment in patients with advanced or metastatic vaginal and vulvar squamous cell carcinomas. Given the rarity of these cancers and the lack of standard second-line therapies, this study explores sac-TMT, a novel TROP-2-directed antibody-drug conjugate (ADC). TROP-2 is highly expressed in both vulvar and vaginal squamous cell carcinomas, making it a promising therapeutic target.
Read the detailed description
RATIONALE AND MOLECULAR TARGETING
Advanced and metastatic vulvar and vaginal squamous cell carcinomas share pathophysiological features with cervical cancer, including high rates of Human Papillomavirus (HPV) driver oncogenesis and robust expression of Trophoblast Cell Surface Antigen 2 (TROP-2). Sacituzumab tirumotecan (sac-TMT, MK-2870) is a novel TROP-2-directed antibody-drug conjugate (ADC) composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked via a methyl sulfonyl moiety to a potent topoisomerase 1 inhibitor payload (KL610023). Upon binding to TROP-2 on tumor cells, sac-TMT internalizes and releases its payload, inducing cell cycle arrest and apoptosis while exerting bystander-killing and antibody-dependent cellular cytotoxicity.
DREAM STUDY DESIGN AND STATISTICAL CONSIDERATIONS
This Phase II study utilizes a Simon's two-stage Minimax design for each independent cohort (Cohort A: Vagina; Cohort B: Vulva) to control the familywise alpha level at 0.05 (one-sided) with 80% power:
Stage 1: 12 participants per cohort will be enrolled. An interim analysis for futility will be conducted; if 0 responses are observed in Stage 1, enrollment in that cohort will be halted.
Stage 2: If $\ge 1$ objective response is achieved in Stage 1, an additional 10 participants will be accrued (totaling 22 evaluable patients per cohort, expanded to 24 to account for a 10% dropout rate). A cohort is considered positive if $\ge 4$ responses are observed among evaluable participants.
TREATMENT ADMINISTRATION AND MANDATORY PROPHYLAXISSac-TMT is administered intravenously on Days 1 and 15 of 28-day cycles. Mandatory premedication administered 1.5 hours ($\pm30$ minutes) prior to each infusion includes an H1 receptor antagonist (diphenhydramine or equivalent), acetaminophen, dexamethasone (8-10 mg IV), and an H2 receptor antagonist to minimize infusion-related reactions. To prevent oral mucositis, participants receive mandatory daily prophylactic steroid-containing mouthwash (dexamethasone solution) 4 times daily. Prophylactic artificial tears are also strongly recommended to mitigate ocular surface toxicities.
EXPLORATORY BIOMARKER RESEARCH
The trial incorporates a longitudinal biorepository to identify predictive signatures and resistance mechanisms. Mandatory archival or freshly obtained FFPE tumor tissue blocks/slides collected at baseline will undergo TROP-2 immunohistochemistry (IHC), p16/HPV16 profiling, and high-throughput next-generation sequencing (NGS). Serial blood samples (plasma/PBMCs) collected at baseline and prespecified on-treatment timepoints (Weeks 6, 12, 24, and at disease progression) will evaluate circulating tumor DNA (ctDNA) dynamics and immune cell profiling to monitor treatment response and genomic resistance patterns over time.
- Being tested
- Sacituzumab Tirumotecan (sac-TMT)
- Keywords
- Sacituzumab Tirumotecan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacituzumab Tirumotecan (sac-TMT)Drug
Also called MK-2870, SKB264
Sacituzumab tirumotecan is a TROP-2-directed antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase 1 inhibitor payload (KL610023). It will be administered intravenously at a dose of $4\text{ mg/kg}$ on Days 1 and 15 of every 28-day cycle until disease progression, unacceptable toxicity, or up to a maximum duration of approximately 2 years.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Vaginal Cancer | Experimental | Participants with advanced or metastatic vaginal squamous cell carcinoma who progressed on or after platinum-based chemotherapy. Participants will receive sacituzumab tirumotecan (sac-TMT, MK-2870) monotherapy at a dose of $4\text{ mg/kg}$ via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or for a maximum exposure duration of approximately 2 years. Receives: Drug: Sacituzumab Tirumotecan (sac-TMT) |
| Cohort B: Vulvar Cancer | Experimental | Participants with advanced or metastatic vulvar squamous cell carcinoma who progressed on or after platinum-based chemotherapy. Participants will receive sacituzumab tirumotecan (sac-TMT, MK-2870) monotherapy at a dose of $4\text{ mg/kg}$ via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or for a maximum exposure duration of approximately 2 years. Receives: Drug: Sacituzumab Tirumotecan (sac-TMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) by Investigator Assessment
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by local site investigator/radiology.
Measured: Up to Week 24
Secondary outcomes (10)
Objective Response Rate by Independent Central Review (ORR-ICR)
Proportion of participants achieving complete response (CR) or partial response (PR) as evaluated by Independent Central Review using RECIST v1.1 criteria.
Measured: Up to 24 weeks.
Disease Control Rate (DCR)
Proportion of participants achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 by investigator assessment..
Measured: Up to 24 weeks.
Duration of Response (DoR)
Time from the first documented evidence of complete response (CR) or partial response (PR) until the date of first documented disease progression or death due to any cause, whichever occurs first.
Measured: Up to approximately 40 months.
Progression-Free Survival (PFS)
Time from the date of enrollment until the date of first documented disease progression (radiographically or clinically confirmed per RECIST 1.1) by investigator assessment, or death due to any cause, whichever occurs first.
Measured: Up to approximately 40 months.
Overall Survival (OS)
Time from the date of enrollment to the date of participant death due to any cause.
Measured: Up to approximately 40 months.
Clinical Benefit Rate (CBR)
Rate, incidence, and severity of treatment-emergent adverse events (AEs) and Grade $\ge 3$ AEs evaluated according to NCI CTCAE version 5.0, including Adverse Events of Special Interest (AESIs).
Measured: From enrollment up to 30 days after the last dose of study intervention.
Treatment Compliance
Assessment of treatment modifications, including the proportion and reasons for dose reductions, treatment delays, or permanent discontinuations (e.g., disease progression, AEs, consent withdrawal).
Measured: Up to approximately 2 years.
Post-Progression Therapies
Descriptive characterization and timing of subsequent anticancer therapies administered after disease progression on sac-TMT.
Measured: Up to approximately 40 months.
Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30
Assessment of changes from baseline in global health status, functional domains, and symptom scales evaluated using the EORTC QLQ-C30 core cancer instrument.
Measured: Baseline and every 6 weeks during treatment up to Week 24.
Health-Related Quality of Life (HRQoL) - EORTC QLQ-VU34
ssessment of changes from baseline in vulvar/vaginal cancer-specific symptoms evaluated using the EORTC QLQ-VU34 questionnaire.
Measured: Baseline and every 6 weeks during treatment up to Week 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2026
- Study startJan 2027 (estimated)
- Primary completionMar 2030 (estimated)
- Study completionJan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vaginal 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Latin American Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fernando Cotait Maluf, Principal investigator, Hospital Israelita Albert Einstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07804966
- Sponsor's protocol ID
- LACOG 1724
- Acronym
- ARCANA
- Status last verified
- Aug 2026
- First submitted
- 1 Sep 2026
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Phase II Trial of Sacituzumab Tirumotecan (Sac-TMT) as Second-line Treatment for Advanced/Metastatic Vaginal and Vulvar Squamous Cell Carcinoma - ARCANA Trial (LACOG 1724)
- ClinicalTrials.gov ID
- NCT07804966
- Acronym / sponsor ID
- ARCANA / LACOG 1724
- Keywords
- Sacituzumab Tirumotecan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Latin American Cooperative Oncology GroupUniversity, hospital or other
- Study start
- Jan 2027 (estimated)
- Primary completion
- Mar 2030 (estimated)
- Study completion
- Jan 2032 (estimated)
- First posted
- 4 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.
The ARCANA trial (LACOG 1724) is a single-arm, non-randomized, multi-center, parallel, two-cohort Phase II clinical study designed to evaluate the efficacy and safety of sacituzumab tirumotecan (sac-TMT, MK-2870) as a second-line or subsequent treatment in patients with advanced or metastatic vaginal and vulvar squamous cell carcinomas. Given the rarity of these cancers and the lack of standard second-line therapies, this study explores sac-TMT, a novel TROP-2-directed antibody-drug conjugate (ADC). TROP-2 is highly expressed in both vulvar and vaginal squamous cell carcinomas, making it a promising therapeutic target.
Detailed description
RATIONALE AND MOLECULAR TARGETING
Advanced and metastatic vulvar and vaginal squamous cell carcinomas share pathophysiological features with cervical cancer, including high rates of Human Papillomavirus (HPV) driver oncogenesis and robust expression of Trophoblast Cell Surface Antigen 2 (TROP-2). Sacituzumab tirumotecan (sac-TMT, MK-2870) is a novel TROP-2-directed antibody-drug conjugate (ADC) composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked via a methyl sulfonyl moiety to a potent topoisomerase 1 inhibitor payload (KL610023). Upon binding to TROP-2 on tumor cells, sac-TMT internalizes and releases its payload, inducing cell cycle arrest and apoptosis while exerting bystander-killing and antibody-dependent cellular cytotoxicity.
DREAM STUDY DESIGN AND STATISTICAL CONSIDERATIONS
This Phase II study utilizes a Simon's two-stage Minimax design for each independent cohort (Cohort A: Vagina; Cohort B: Vulva) to control the familywise alpha level at 0.05 (one-sided) with 80% power:
Stage 1: 12 participants per cohort will be enrolled. An interim analysis for futility will be conducted; if 0 responses are observed in Stage 1, enrollment in that cohort will be halted.
Stage 2: If $\ge 1$ objective response is achieved in Stage 1, an additional 10 participants will be accrued (totaling 22 evaluable patients per cohort, expanded to 24 to account for a 10% dropout rate). A cohort is considered positive if $\ge 4$ responses are observed among evaluable participants.
TREATMENT ADMINISTRATION AND MANDATORY PROPHYLAXISSac-TMT is administered intravenously on Days 1 and 15 of 28-day cycles. Mandatory premedication administered 1.5 hours ($\pm30$ minutes) prior to each infusion includes an H1 receptor antagonist (diphenhydramine or equivalent), acetaminophen, dexamethasone (8-10 mg IV), and an H2 receptor antagonist to minimize infusion-related reactions. To prevent oral mucositis, participants receive mandatory daily prophylactic steroid-containing mouthwash (dexamethasone solution) 4 times daily. Prophylactic artificial tears are also strongly recommended to mitigate ocular surface toxicities.
EXPLORATORY BIOMARKER RESEARCH
The trial incorporates a longitudinal biorepository to identify predictive signatures and resistance mechanisms. Mandatory archival or freshly obtained FFPE tumor tissue blocks/slides collected at baseline will undergo TROP-2 immunohistochemistry (IHC), p16/HPV16 profiling, and high-throughput next-generation sequencing (NGS). Serial blood samples (plasma/PBMCs) collected at baseline and prespecified on-treatment timepoints (Weeks 6, 12, 24, and at disease progression) will evaluate circulating tumor DNA (ctDNA) dynamics and immune cell profiling to monitor treatment response and genomic resistance patterns over time.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Vaginal Cancer | Experimental | Drug: Sacituzumab Tirumotecan (sac-TMT)Participants with advanced or metastatic vaginal squamous cell carcinoma who progressed on or after platinum-based chemotherapy. Participants will receive sacituzumab tirumotecan (sac-TMT, MK-2870) monotherapy at a dose of $4\text{ mg/kg}$ via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or for a maximum exposure duration of approximately 2 years. |
| Cohort B: Vulvar Cancer | Experimental | Drug: Sacituzumab Tirumotecan (sac-TMT)Participants with advanced or metastatic vulvar squamous cell carcinoma who progressed on or after platinum-based chemotherapy. Participants will receive sacituzumab tirumotecan (sac-TMT, MK-2870) monotherapy at a dose of $4\text{ mg/kg}$ via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle. Treatment continues until disease progression, unacceptable toxicity, or for a maximum exposure duration of approximately 2 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Has a histologically- or cytologically confirmed diagnosis of squamous cell carcinoma of vagina (cohort A) or vulvar (cohort B) origin
- Advanced disease, defined as presence of metastatic disease or locally advanced disease not amenable to curative therapy in the opinion of the investigator
- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions.
- Has received up to 2 prior lines of systemic therapy. Disease progression to first-line or second-line platinum-based chemotherapy for locally advanced/metastatic disease. Previous anti-PD-1/anti-PD-L1 therapy is allowed. Disease progression within 6 months of (neo) adjuvant chemotherapy completion is considered first-line of therapy. The participant may have received prior radiation with or without radio-sensitizing chemotherapy at least >2 weeks before the start of study treatment.
- At least 18 years of age at the time of providing informed consent.
Key exclusion criteria (23 listed)
- Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
- Refer to Section 6.2 for information on COVID-19 vaccines.
- Note: A list of strong inducers/inhibitors of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally-approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor of CYP3A4. Prior/Concurrent Clinical Study Experience
- Other Exclusions
- Note: Participants who underwent major surgery must have adequately recovered from toxicity and/or complications from the surgery before starting study intervention.
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 |
|---|---|---|
| Sacituzumab Tirumotecan (sac-TMT)Also: MK-2870, SKB264Sacituzumab tirumotecan is a TROP-2-directed antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase 1 inhibitor payload (KL610023). It will be administered intravenously at a dose of $4\text{ mg/kg}$ on Days 1 and 15 of every 28-day cycle until disease progression, unacceptable toxicity, or up to a maximum duration of approximately 2 years. | Drug | Cohort A: Vaginal Cancer, Cohort B: Vulvar Cancer |
Primary outcome
Objective Response Rate (ORR) by Investigator Assessment
Time frame: Up to Week 24
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by local site investigator/radiology.
10 secondary outcomes
Objective Response Rate by Independent Central Review (ORR-ICR)
Time frame: Up to 24 weeks.
Disease Control Rate (DCR)
Time frame: Up to 24 weeks.
Duration of Response (DoR)
Time frame: Up to approximately 40 months.
Progression-Free Survival (PFS)
Time frame: Up to approximately 40 months.
Overall Survival (OS)
Time frame: Up to approximately 40 months.
Clinical Benefit Rate (CBR)
Time frame: From enrollment up to 30 days after the last dose of study intervention.
Treatment Compliance
Time frame: Up to approximately 2 years.
Post-Progression Therapies
Time frame: Up to approximately 40 months.
Health-Related Quality of Life (HRQoL) - EORTC QLQ-C30
Time frame: Baseline and every 6 weeks during treatment up to Week 24.
Health-Related Quality of Life (HRQoL) - EORTC QLQ-VU34
Time frame: Baseline and every 6 weeks during treatment up to Week 24.
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 4 Sep 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.
Fernando Cotait Maluf principal investigator
Hospital Israelita Albert Einstein
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacituzumab Tirumotecan (sac-TMT) in people with Vaginal Squamous Cell Carcinoma and Vulvar Squamous Cell Carcinoma, run by Latin American Cooperative Oncology Group at 12 sites in Brazil.
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 23 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 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Brazil. 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 Project Manager (+55 (51) 3384.5334, lacog1724@lacog.group), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) by Investigator Assessment (time frame: Up to Week 24). 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 4 Sep 2026.