Using sacituzumab govitecan for treating relapsed ovarian, endometrial, and cervical cancers

Phase II Pilot Study of Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas

This study is testing if a new treatment called sacituzumab govitecan can help people with relapsed ovarian, endometrial, and cervical cancers feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 95 (estimated)
• Ages: 18 Years to 120 Years
• Sex: Female
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: bevacizumab, chemotherapy, immunotherapy, radiation, sacituzumab
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06865677 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of sacituzumab govitecan (SG), an antibody-drug conjugate targeting TROP2, in patients with recurrent platinum-resistant ovarian, endometrial, or cervical cancers. Participants aged 18 and older will undergo screening, including physical exams, imaging scans, and biopsies, to confirm eligibility. SG will be administered through intravenous infusion in 21-day cycles, with treatment occurring on days 1 and 8 of each cycle. The primary objective is to determine the objective response rate of SG in these specific cancer types.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recurrent platinum-resistant ovarian, endometrial, or cervical cancers who have undergone at least two prior systemic treatments.

Not a fit: Patients with cancers that are not platinum-resistant or those who have not received prior systemic therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat relapsed gynecologic cancers.

How similar studies have performed: Other studies have shown promise with similar antibody-drug conjugate approaches, but this specific application of sacituzumab govitecan in these cancer types is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

Cohort 1 (Ovarian Cancer)

* Participants must have histologically or cytologically confirmed recurrent platinum-resistant (defined as less than six months of platinum-free interval) epithelial (i.e., high grade serous, endometrioid, low grade serous, or clear cell) ovarian carcinoma that is refractory to standard treatment.
* Participants with known BRCA mutated tumors should have received a PARP inhibitor maintenance or treatment.
* Participants without known BRCA mutation and platinum-resistant tumors must have had prior bevacizumab or not eligible for bevacizumab-based therapy (i.e., history of proteinuria).

Cohort 2 (Endometrial Cancer)

* Participants must have histologically or cytologically confirmed recurrent epithelial (i.e., endometrioid or serous) endometrial carcinoma that is refractory to standard treatment.
* Participants must have received prior anti-PD-1/PD-L1-based therapy or not eligible for anti-PD-1/PD-L1-based therapy.

Cohort 3 (Cervical Cancer)

-Participants must have histologically or cytologically confirmed recurrent epithelial cervical (i.e. squamous or adeno) carcinoma that is refractory to standard treatment.

Note: Participants with a history of human papilloma virus infection (i.e., positive HPV DNA testing) are eligible.

-Participants must have received prior bevacizumab-based therapy or not eligible for bevacizumab-based therapy (i.e., history of proteinuria).

Note: Platinum chemotherapy administered concurrent with primary radiation (i.e., weekly cisplatin) is not counted as a systemic chemotherapeutic regimen for management of persistent or recurrent carcinoma of the cervix.

All Cohorts

* Participants must have received at least two systemic therapies including at least one platinum-based therapy regimen.
* Participants must have radiographically measurable disease, per RECIST 1.1, and safely biopsiable lesion.
* Age \>= 18 years
* ECOG performance status \<= 1
* Adequate organ and marrow function as defined below:

  * Hemoglobin (Hgb) \>= 9.0 g/dL
  * Absolute neutrophil count (ANC) \>= 1,500/mcL
  * Platelets \>= 100,000/mcL
  * White Blood Cell count (WBC) \>= 3,000/mcL
  * Total bilirubin \<= 1.5 x upper limit of normal (ULN) (\<= 3 x ULN in participants with known/suspected Gilbert s disease)
  * Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \<= 2.5 x ULN
  * Serum creatinine \<= 1.5 x ULN or estimated GFR \>= 30 ml/min/1.73 m\^2
* Participants with suspicion or prior history of treated central nervous system (CNS) metastases with no evidence of active disease (assessed by MRI or contrast CT scan of the brain and spinal column) are eligible if pretreatment brain MRI demonstrate no evidence of disease in the past 4 weeks prior to entry.
* Major surgical procedure, other than for diagnosis, must not occur within 4 weeks prior to the first dose of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the study drug.
* Participants with prior cancer-directed therapy must have a washout period of 3 weeks prior to the first dose of study treatment.
* Participants with prior cancer-directed immunotherapy-based therapy must have a washout period of 4 weeks prior to the first dose of study treatment.
* Human immunodeficiency virus (HIV)-infected participants are eligible if on stable dose of highly active antiretroviral therapy (HAART), a CD4 count \>= 200 cells/mcL, and an undetectable viral load (VL).
* Hepatitis B virus (HBV) positive participants are eligible if they have been treated or are on an appropriate course of antivirals at study entry.
* Participants with a history of hepatitis C virus (HCV) infection (i.e., positive HCV antibody test) must have been treated and cured (undetectable HCV VL at screening). Participants with HCV infection who are currently on treatment are eligible if they have an undetectable HCV VL.
* Individuals of child-bearing potential (IOCBP) must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after the last dose of study drug.
* IOCBP must undergo pregnancy testing at screening and must not be pregnant in order to take part. Note: In these cases, a negative Beta-human chorionic gonadotropin (Beta-hCG) (urine or blood) is required.
* Nursing participants must discontinue nursing and/or not begin nursing until 1 month after the last dose of study drug.
* Ability of participants to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* Participants who are receiving any other investigational agents
* Primary platinum-refractory ovarian cancer (defined as progression while on the upfront platinum-based therapy)
* Participants with any other concomitant invasive malignancies
* History of severe hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to SG, SN-38, or irinotecan.
* Prior treatment with TROP2-targeting ADC. Participants with prior use of other ADCs are eligible.
* Prior treatment with topoisomerase 1 inhibitors i.e., topotecan
* Symptomatic or untreated brain/CNS metastases
* Participants who require treatment with UGT1A1 inhibitors.
* Participants with known homozygous UGT1A1\*28 allele if tested during the previous treatment.
* Participants with active infection requiring antibiotics.
* Participants who have not recovered from toxicities or AEs related to prior therapy to Grade \<= 1 with the following exceptions.

  * Participants with platinum related hypomagnesemia (on replacement) are eligible.
  * Participants with auto-immune thyroid dysfunction on stable replacement therapy are eligible.
  * Participants with any grade alopecia or grade 1 or 2 neuropathy are eligible.
* Participants with a history of gastrointestinal (GI) perforation or hemorrhage (\> 30mL bleeding/episode) fistula or hemoptysis within 3 months prior to initiation of study therapy, intra-abdominal abscess in the 6 months prior to entry, history of ascites or pleural effusion requiring paracentesis or thoracentesis in the 4 weeks prior to initiation of study therapy or history of bowel obstruction within 3 months prior to initiation of study therapy.
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during SG treatment or within 5 months after the final dose of SG. Note: Seasonal flu vaccines that do not contain a live virus and locally authorized/approved COVID-19 vaccines are permitted
* Participants with severe uncontrolled intercurrent illness that would limit compliance with study requirements, evaluated by history, physical exam, and chemistry panel.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Jung-Min Lee, M.D. — National Cancer Institute (NCI)
• Study coordinator: Ann C McCoy, R.N.

Conditions Recurrent Platinum Resistant Epithelial Ovarian Carcinoma; Recurrent Epithelial Endometrial Carcinoma; Recurrent Epithelial Cervical Carcinoma; TROP2; ADC; Gynecologic Malignancies; Relapsed