A Phase I/II Open Label Study of the Safety and Efficacy of Apatinib Administered to Patients With Advanced Malignancies to Improve Sensitivity to Pembrolizumab in the Second- or Later-line Setting (APPEASE)

University of Utah1 site in 1 country5 target enrollmentJune 19, 2018

ConditionsAdvanced Malignancies Urothelial Carcinoma MSI-H or dMMR Solid Tumors Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

InterventionsApatinib Pembrolizumab

DrugsApatinib Pembrolizumab

Overview

Phase: Phase 1
Intervention: Apatinib
Conditions: Advanced Malignancies
Sponsor: University of Utah
Enrollment: 5
Locations: 1
Primary Endpoint: Incidence of dose limiting toxicities (DLTs) of Apatinib in combination with pembrolizumab
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open label nonrandomized Phase I/ IIA trial designed to assess the safety, tolerability, and efficacy of apatinib in combination with pembrolizumab. Phase I will assess the safety of combining increasing oral daily doses of apatinib with a fixed dose of IV pembrolizumab every three weeks and will determine the RP2D (Recommended Phase 2 Dose). Phase II will assess the efficacy of the RP2D of apatinib in combination with pembrolizumab and provide additional safety and tolerability data in three disease-specific cohorts

Registry

clinicaltrials.gov

Start Date

June 19, 2018

End Date

July 2, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Utah

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female subject aged ≥ 18 years.
•One of the following advanced solid malignancies which qualifies for standard of care pembrolizumab treatment per FDA approval:
•Locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant/adjuvant platinum-based therapy. Patients may have received any amount of platinum-based therapy.
•Unresectable or metastatic MSI-H or dMMR solid tumors that have progressed during or following prior treatment and have no satisfactory alternative treatment options (including MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan).
•Recurrent locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (as determined by an FDA-approved test) that have progressed on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.
•Patients must have available and be willing to provide formalin fixed paraffin embedded tissue sample from archival tissue (patients who can't provide archival tissue will be offered an optional biopsy; lack of tissue will not be exclusionary).
•Have measurable disease based on RECIST 1.
•(For Phase 2 Subjects Only)
•Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive, a serum pregnancy test will be required.
•Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for at least 1 year.

Exclusion Criteria

•Previous treatment with and disease progression on a combination of a VEGF inhibitor and an immune checkpoint inhibitor. Patients who have been treated with and have progressed on a single agent VEGF inhibitor OR an immune checkpoint inhibitor will not be excluded.
•Current use of immunosuppressive medication, EXCEPT for the following:
•Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids.
•Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone equivalent.
•Steroids as premedication for hypersensitivity reactions.
•Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent per treating physician's clinical judgment. Subjects with type 1 diabetes, vitiligo, psoriasis, hypothyroidism, or hyperthyroidism not requiring immunosuppressive medications are eligible.
•Prior organ transplant including allogenic hematopoietic stem cell transplant.
•Active infection requiring intravenous antibiotics (must be completed prior to registration).
•Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
•Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

Arms & Interventions

Apatinib and Pembrolizumab, all patients

Intervention: Apatinib

Apatinib and Pembrolizumab, all patients

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

Incidence of dose limiting toxicities (DLTs) of Apatinib in combination with pembrolizumab

Time Frame: 21 days, one cycle

Safety and tolerability of apatinib (rivoceranib) in combination with pembrolizumab in subjects with select advanced malignancies (urothelial carcinoma, MSI-H/dMMR solid tumors including colorectal cancer, and gastric or gastroesophageal junction GEJ adenocarcinoma) and determine the recommended Phase II dose (RP2D) for apatinib in combination with pembrolizumab. Adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs)

Objective Response Rate (ORR) (Phase II)

Time Frame: 12 months

Objective response rate (ORR) by RECIST 1.1

Secondary Outcomes

Progression Free Survival (PFS)(5 years (Patients are expected to stay on treatment for approximately 12 months))
Occurrence of Adverse Events and Serious Adverse Events(12 months)