Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Endometrial Neoplasms

Disease Attributes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine

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.

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

pembrolizumab

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

Sitravatinib

Haider Mahdi, MD

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.

This trial hypothesizes that adding anti-angiogenesis therapy to anti-PD1 therapy will reverse PD1 resistance and improve response to immunotherapy with immune checkpoint inhibitors in patients with recurrent endometrial cancer 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 at 100 mg. Treatment will continue until disease progression or unacceptable toxicities. For patients with a complete response to therapy, maintenance therapy with both drugs will be continued for 12 months after achieving complete response. The combination of pembrolizumab with sitravatinib is an attractive treatment approach for this patient population. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2, and selected Eph family members. In addition to the immunostimulatory effects of Axl and MET inhibition, sitravatinib may further condition the TME in favor of antitumor activity by its immunomodulatory effects mediated through VEGFR and KIT inhibition.

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

Pembrolizumab With Sitravatinib in Recurrent Endometrial Cancer and Other Solid Tumors With Deficient Mismatch Repair System Post PD1 Exposure: Phase II Trial

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.

Proportion of participants with complete response, partial response and stable disease 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Time from first response to to treatment until documented disease progression by RECIST v1.1 or death due to any cause. Progressive Disease (PD) as defined by RECIST v1.1 for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions, (PD): Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Time from start of complete or partial response until documented disease progression by RECIST v1.1, or death due to any cause. Progressive Disease (PD) as defined by RECIST v1.1 for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions, (PD): Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Time from first dose of study treatment until death due to any cause.

Proportion of participants with confirmed Complete Response (iCR) or Partial Response (iPR) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Complete Response (iCR), which describes the complete disappearance of TL and Non-TL. All lymph nodes must be non-pathological in size (\< 10 mm in SAD). Partial Response (iPR), which occurs when the tumor load of the TL is reduced by ≤30% compared to the baseline, or in the case of complete remission of the TL, when one or more Non-TL can still be distinguished.

Adverse Events which occur from first day of treatment, characterized by type, grade and relatedness to treatment according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0, considered to be possibly, probably or definitely related to study treatment.

Spots Global Cancer Trial Database for deficient mismatch repair system (dmmr)