Dostarlimab in Chemoresistant Gestational Trophoblastic Neoplasia

This is an interventional treatment trial for Gestational Trophoblastic Neoplasia Read More

Inclusion Criteria:

1. Patients with persistent unresectable Gestational Trophoblastic Neoplasia (GTN) disease following 2 lines of single agent chemotherapy or persistent or recurrent disease following 1 line of multi-agent chemotherapy.
2. Female patients >18 years old.
3. Pretreatment archival tissue (if available) must be submitted for correlative studies. If pre-treatment tissue is not available, this does not exclude the patient.
4. Patients must have recovered from the effects of recent surgery or radiotherapy (persistent toxicity, CTCAE grade ≤1 except for alopecia, sensory neuropathy, or fatigue).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Patients must have elevated hCG or measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

7. Patients must have adequate organ function.

   1. Absolute neutrophil count ≥ 1,500/ microliter (µL)
   2. Platelets ≥ 100,000/µL
   3. Hemoglobin ≥ 9 g/ deciliter (dL)
   4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 milliliters (mL)/min using the Cockcroft-Gault equation
   5. Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
   6. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
   7. International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants.
   8. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

8. If of childbearing potential, must agree to use a highly effective contraceptive method or abstain from activities that could result in pregnancy from enrollment through 150 days after the last dose of study treatment or be of non-child bearing potential. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Non-child bearing potential is defined as follows (by other than medical reasons):

   • ≥45 years of age and has not had menses for >1 year
   • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
   • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use a highly effective contraception method throughout the study, starting with signing the Informed Consent Form (ICF) through 150 days after the last dose of study treatment. See Section 4.11 for a list of highly effective birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
9. Participant of childbearing potential must have the treating physician document that positive pregnancy test does not represent a clinically viable pregnancy.
10. Participant must agree to not breastfeed during the study or for 150 days after the last dose of study treatment.
11. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
12. Life expectancy of at least 16 weeks.

Exclusion Criteria:

1. Prior therapy with anti-Programed Death (PD)1/Programed Death Ligand-1 (PD-L1) or anti-CTLA4 antibody
2. Participant must not be simultaneously enrolled in any interventional clinical trial.
3. Participant must not have had major surgery ≤3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
4. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
5. Participant must not have a known hypersensitivity to dostarlimab components or excipients.
6. Participant must not have a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
7. Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the Investigator.
8. Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
9. Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
10. Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (HCV) (e.g., hepatitis C virus (HCV) ribonucleic acid [qualitative] is detected).
11. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
12. Participant must not have a history of interstitial lung disease.
13. Participant is considered a poor medical risk that would interfere with cooperation with the requirements of the study.
14. Participant has received a live vaccine within 30 days of before first dose of study treatment.
15. Subject is pregnant or breastfeeding or is expecting to conceive children within the projected duration of the study, through 150 days after the last dose of study treatment.