Clinical trial NCT06865677: Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas
Official title: Phase II Pilot Study of Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Platinum Resistant Epithelial Ovarian Carcinoma
Recurrent Epithelial Endometrial Carcinoma
Recurrent Epithelial Cervical Carcinoma
Keywords: TROP2
ADC
Gynecologic Malignancies
Relapsed
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2025-03-10
Enrollment: 95
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Background:

Cancers of the female reproductive organs often come back after treatment. A drug called sacituzumab govitecan (SG) has been approved for use in other types of cancers. Researchers want to see if SG can also help people with ovarian, endometrial, or cervical cancers.

Objective:

To test SG in people with ovarian, endometrial, or cervical cancers.

Eligibility:

People aged 18 years and older with ovarian, endometrial, or cervical cancer. Their cancers must have returned after at least 2 rounds of standard treatments.

Design:

Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. They also will have biopsies to get new tissues samples taken from their tumors.

SG is infused through a tube attached to a needle inserted into a vein in the arm. Treatment will be given in 21-day cycles. Participants will receive SG on days 1 and 8 of each cycle. Each infusion takes 1 to 3 hours.

Participants may receive SG for up to 5 years. They can continue as long as the drug is helping them. Imaging scans and other tests will be repeated throughout the study period.

Participants will have an end-of-treatment visit within 2 weeks and a safety visit about 30 days after they stop treatment. Physical exams, blood tests, and imaging scans may be repeated.

Participants will then be contacted by phone every 6 months for up to 10 years after their first dose of SG.

Sponsoring Institution:

National Cancer Institute

Detailed description: Background:

* Human trophoblast cell-surface marker (TROP2) is a surface glycoprotein originally identified in human placental tissue and highly expressed in gynecologic malignancies. TROP2 overexpression in ovarian, endometrial, and cervical cancers is linked to tumorigenicity and poor overall survival.
* Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) of an IgG(kappa)1 monoclonal antibody targeting TROP2 with a chemotherapeutic payload of SN-38. SN-38 is an active metabolite of irinotecan and acts as a topoisomerase I inhibitor.
* Preclinical data suggest that SG induces DNA damage, replication stress, and tumor shrinkage in drug-resistant ovarian, endometrial, and cervical cancer in vitro and in vivo preclinical models.
* Further clinical and translational studies are needed to better understand SG s clinical activity and biology in relapsed gynecologic cancer patients.

Objective:

-To determine the objective response rate (ORR) of sacituzumab govitecan (SG) in participants with recurrent gynecological malignancies, calculated for each individual tumor histology by RECIST v1.1.

Eligibility:

* Age \>= 18 years
* ECOG performance status \<= 1
* Histologically documented, recurrent platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer (referred to as ovarian cancer); recurrent endometrioid or serous endometrial cancer; or recurrent epithelial cervical cancer
* At least two prior systemic therapeutic regimens
* Measurable disease by RECIST v1.1 criteria with lesions that can be safely biopsied
* No prior TROP2-targeting ADC

Design:

* This is an open label, non-randomized Phase II pilot study with one Arm.
* SG will be administered intravenously (IV) at 10 mg/kg on Days 1 and 8 each 21-day cycle.
* Tumor assessments will be time-based: every 9 weeks (+/- 1 week) for the first year and every 12 weeks (+/- 1 week) thereafter until disease progression. Pre-treatment biopsies and serial blood samples will be collected for the correlative studies.
* Treatment will be given for a maximum of 5 years or until disease progression or unacceptable toxicities.
* Up to 66 evaluable participants will be enrolled.

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.

Primary outcomes:
measure: Determine the ORR of SG in participants with recurrent gynecological malignancies, calculated for each individual tumor histology by RECIST v1.1
timeFrame: CT/MRI every 9 weeks (+/- 1 week) for the first year and then every 12 weeks (+/-1 week) until progressive disease or up to 5 years and at end of treatment which occurs within 14 days after the end of therapy.
Secondary outcomes:
measure: Determine the median DoR of SG
timeFrame: Every 9 weeks for the first year and then every 12 weeks until progressive disease or up to 5 years and at end of treatment which occurs within 14 days after the end of therapy.
measure: Determine the Overall Survival of participants receiving SG
timeFrame: Days 1, 8, and 15 of each cycle for up to 5 years, at end of treatment (within 14 days after the end of therapy), 30-day safety visit and every 6 months during follow up
measure: Determine the PFS of participants receiving SG
timeFrame: Every 9 weeks for the first year and then every 12 weeks until PD or up to 5 years and at EOT which occurs within 14 days after the end of therapy.
measure: Determine the safety of SG
timeFrame: Days 1, 8, and 15 of each cycle, at end of treatment (within 14 days after), and 30 days after the end of treatment. Beyond 30 days after the last intervention only adverse events which are serious and related to the study intervention will be assessed.
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Jung-Min Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: