Sac-TMT in Vaginal and Vulvar Cancers

NCT07804966 | Not Yet Recruiting Phase 2

• 1 other identifier: LACOG 1724
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 12

Brief 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 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.

Conditions

Vaginal Squamous Cell Carcinoma; Vulvar Squamous Cell Carcinoma

Keywords

Sacituzumab Tirumotecan

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to Week 24

Secondary Outcomes (10)

• Objective Response Rate by Independent Central Review (ORR-ICR)

  Up to 24 weeks.

• Disease Control Rate (DCR)

  Up to 24 weeks.

• Duration of Response (DoR)

  Up to approximately 40 months.

• Progression-Free Survival (PFS)

  Up to approximately 40 months.

• Overall Survival (OS)

  Up to approximately 40 months.

Study Arms (2)

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.

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.

Drug: Sacituzumab Tirumotecan (sac-TMT)

Interventions

Sacituzumab Tirumotecan (sac-TMT) DRUG

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.

Also known as: MK-2870, SKB264

Cohort A: Vaginal Cancer; Cohort B: Vulvar Cancer

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.
• \. 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.
• \. Adequate organ function as defined in the following table (Table 2). Specimens must be collected within 14 days before the start of study intervention.
• \. 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.
• \. 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead

Study Sites (12)

Pronutrir - Suporte Nutricional e Quimioterapia

Fortaleza, Ceará, 60810-180, Brazil

Location

Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel (Oncoclínicas)

Salvador, Estado de Bahia, 40050-410, Brazil

Location

HIAE - Hospital Israelita Albert Einstein

São Paulo, HIAE - Hospital Israelita Albert Einstein, 05653-000, Brazil

Location

UFMG - Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Hospital Napoleão Laureano

João Pessoa, Paraíba, 58013-140, Brazil

Location

Hospital Ophir Loyola

Belém, Pará, 66063-240, Brazil

Location

Centro de Pesquisa Vencer e Oncoclínica

Teresina, Piauí, 60449-200, Brazil

Location

INCA - Instituto Nacional de Câncer

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

Location

Liga Norte Riograndense Contra o Câncer

Natal, Rio Grande do Norte, 59062-000, Brazil

Location

Futtura Oncologia - Hub de Pesquisa Clínica

Porto Alegre, Rio Grande do Sul, 90470-340, Brazil

Location

ICESP - Instituto do Câncer do Estado de São Paulo

São Paulo, São Paulo, 01246-000, Brazil

Location

FUNFARME - Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paul, 15090-000, Brazil

Location

Study Officials

• Fernando Cotait Maluf

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager

CONTACT

+55 (51) 3384.5334; lacog1724@lacog.group

Head of Clinical Operations

CONTACT

+55 (51) 3384.5334; laura.voelcker@lacog.group

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 4, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): January 1, 2032
• Last Updated: September 4, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (12)