Pembrolizumab With Sitravatinib in Recurrent Endometrial Cancer and Other Solid Tumors With Deficient Mismatch Repair System

NCT05419817 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCC 21-192
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study of pembrolizumab in combination with sitravatinib in adult women with recurrent endometrial cancer or other solid tumors with deficient mismatch repair system. All patients enrolled will receive pembrolizumab as standard of care combined with Sitravatinib, which will be self-administered orally daily.

Conditions

Recurrent Endometrial Cancer; Solid Tumors

Keywords

deficient mismatch repair system (dMMR); VEGFR and KIT inhibition; anti-PD-1 therapy; checkpoint blockade

Outcome Measures

Primary Outcomes (1)

• Objective Response

  Proportion of participants with confirmed complete response or partial response by RECIST 1.1. Per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  At 12 weeks

Secondary Outcomes (6)

• Clinical Benefit

  Up to 5 years

• Progression-free survival (PFS)

  Up to 5 years

• Duration of Response (DOR)

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

• Objective response irRECIST

  At 12 weeks

Study Arms (1)

Pembrolizumab + Sitravatinib

EXPERIMENTAL

Standard of care pembrolizumab 200 mg IV combined with oral sitravatinib 100 mg oral QD every 21 days until disease progression, unacceptable toxicities or complete response.

Drug: pembrolizumab; Drug: Sitravatinib

Interventions

pembrolizumab DRUG

Pembrolizumab is an immunotherapy (monoclonal antibodies) that will be given at a dosage of 200 mg IV, on Day 1 of each 21 day treatment cycle

Also known as: Keytruda®

Pembrolizumab + Sitravatinib

Sitravatinib DRUG

A small molecule inhibitor of multiple tyrosine kinases that will be taken at a dosage of 100 mg orally, every day

Pembrolizumab + Sitravatinib

Eligibility Criteria

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

You may qualify if:

• Subjects must have recurrent endometrial cancer or other solid tumors with deficient mismatch repair system. Mismatch repair deficiency is defined by 1. Immunohistochemistry with loss of expression of one of these proteins in tumor tissue as defined by standard of care: MLH1, MSH2, MSH6 and PMS2, 2. Microstaellite (MSI) unstable by PCR per standard of care, 3. MSI high by next generation sequencing using commercial platform specifically CARIS, TEMPUS or Foundation testing.
• Must have had prior therapy with a PD1 inhibitor, pembrolizumab or other PD1/PDL1 inhibitor with confirmed radiographic progression of disease while on pembrolizumab or other PD1/PDL1 therapy.
• Up to 5 prior lines of therapy are allowed.
• Prior anti-angiogenesis therapy is not allowed except for bevacizumab. Prior therapy with bevacizumab is allowed.
• Subjects must have measurable disease based on RECIST 1.1 with at least one target lesion.
• Subjects must have an ECOG performance status of 0-1.
• Subjects must be age \>18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with sitravatinib in subjects ≤18 years of age, children are excluded from this study.
• Subjects must have normal organ and marrow function as defined below within 14 days of enrollment unless otherwise indicated:
• Hemoglobin ≥ 9.0 g/dl (may have been transfused)
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range
• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN orAST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
• Estimated Creatinine clearance ≥ 40 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• TSH within normal institutional limits. If elevated, patient can be eligible if evaluated by an endocrine specialist, placed on replacement therapy and deemed eligible with no current or prior autoimmune disease.

You may not qualify if:

• The presence of any of the following will exclude a subject from study enrollment.
• Patients with sarcoma or carcinosarcoma
• Mismatch repair proficient tumors
• Prior anti-cancer therapy within 3 weeks prior to study enrollment.
• Prior surgery or radiation within 3 weeks prior to study enrollment. Cancer directed surgery or radiation are not allowed during treatment.
• Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable with evidence of no disease progression for 6 months.
• Patients having received prior therapy with CTLA4 inhibitors or other immunotherapeutic agents except pembrolizumab or other anti-PD1/PDL1 therapy.
• Patients having received prior anti-angiogenesis therapy (anti-VEGF therapy). Prior bevacizumab therapy is allowed.
• Bowel obstruction (with or without gastrostomy tube) or inability to take oral medications
• Patients with a prior or current bowel perforation or fistula
• Uncontrolled hypertension defined as 140/90mmHg or greater despite medical management with multiple medications
• Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Patients currently on immunosuppressive therapy except:
• Intra-nasal, inhaled, topical or local steroid injections (e.g., intra-articular injection)
• Steroids as premedication for hypersensitivity reaction (e.g., CT scan premedication)."

Sponsors & Collaborators

• Haider Mahdi: lead
• Mirati Therapeutics Inc.: collaborator

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab; sitravatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Haider Mahdi, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 15, 2022
• Study Start: September 8, 2022
• Primary Completion: July 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 27, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share