Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Head and Neck Neoplasms

Carcinoma, Renal Cell

Lung Neoplasms

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles

MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.

MGCD516

Richard Chao, MD

MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles.

During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations.

Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.

During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.

During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon the following cancer diagnosis:

Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL.

Head and neck squamous cell carcinoma with genetic alterations in MET.

Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.

Metastatic prostate cancer with bone metastases.

Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.

Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer

A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies

Proteins include VEGF A, soluble VEGF-R2 and soluble MET

Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Mirati Therapeutics Inc.

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Nivolumab

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.

Sitravatinib oral capsule administered daily for 6-8 weeks in segments 1 and 2.

Sitravatinib

Nivolumab administered as 240 mg IV every 2 weeks for 4-6 weeks in segment 2.

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of nivolumab.

Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma

A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma

Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.

Number and percentage of participants who experienced a response prior to surgery in accordance with RECIST 1.1.

* CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease;
* PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions;
* Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD);
* PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.

TEAEs occured after the first dose of any study treatment or any preexisting condition that increased in severity after the first dose of study treatment and prior to 28 days after last dose of study drug or surgery, whichever occurred last.

TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

The blood plasma concentrations of sitravatinib were determined using blood samples. Blood samples for analysis of blood plasma concentrations of sitravatinib were taken after scheduled vital signs and triplicate electrocardiogram assessments.

Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.

DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.

Tumor tissue was collected from study biopsies and surgical samples. Tumor tissue was used to assess the mean PD-L1 expression in the tumor via immunohistochemistry and/or immunofluorescence.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean ratio of Type 1 to Type 2 tumor associated macrophages using immunohistochemistry.

Cytokines measured in peripheral blood were soluble CD27 (sCD27), eotaxin, macrophage inflammatory protein 1b (MIP-1b), and soluble programmed cell death protein 1 (sPD-1).

Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).

Sitravatinib 120 mg

Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).

Sitravatinib 80 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

EGOG performance status was measured on a 6 point scale to assess participant's performance status.

0: Fully active, able to carry on all pre-disease performance without restriction

1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

Eastern Cooperative Oncology Group (ECOG) Performance Status

T = Size of original tumour, classed from T0 to T4; N = Degree of spread to lymph nodes classed from N0 to N3; M = Presence of distant metastasis classed as M0 to M1. X denotes uncertainty in assigning a given category (T, N, or M) when all reasonable clinical or pathologic maneuvers have been used in staging.

Clinical TNM Staging at Diagnosis

Safety population: all participants who received at least 1 dose of either sitravatinib or nivolumab.

Sr. Clinical Operations Trial Manager

Clinical activity evaluable population: All participants who 1) had measurable disease (per RECIST 1.1) at baseline, 2) received at least one dose of both sitravatinib and nivolumab, 3) had their onstudy disease assessment prior to surgery, and 4) underwent surgery and were deemed disease-free (i.e. non-metastatic) after surgery.

Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery

Preoperative timepoint response: CR

Preoperative timepoint response: PR

Preoperative timepoint response: SD

Preoperative timepoint response: PD

Point in Time Objective Response Prior to Surgery

Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

Day 1 (pre-dose)

Day 1 (30 mins post-dose)

Day 1 (4 hours post-dose)

Day 15 (pre-dose)

Day 43 (pre-dose)

PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 120 mg of sitravatinib orally.

PK Population: Sitravatinib 120 mg

PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 80 mg of sitravatinib orally.

PK Population: Sitravatinib 80 mg

PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 60 mg of sitravatinib orally. This participant was randomized to sitravatinib 120 mg arm, but received sitravatinib 60 mg at Day 43.

PK Population: Sitravatinib 60 mg

Pharmacokinetics (PK) evaluable population: all participants who received treatment with sitravatinib and had non-missing concentration-time data. Concentration was assessed by actual dose associated with each time-point. One participant was randomized to sitravatinib 120 mg arm, but received sitravatinib 60 mg at Day 43.

Blood Plasma Concentrations of Sitravatinib

Time to Surgery

Delays in Surgery

Disease Free Survival (DFS)

Pharmacodynamic evaluable population: all participants who received at least 1 dose of sitravatinib or nivolumab for whom sufficient pharmacodynamic data were available for analysis of the endpoint.

Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor

Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor

Change From Baseline in Regulatory T-cells (Tregs) in the Tumor

Change From Baseline in CD4+ T-cells in the Tumor

Change From Baseline in CD8+ T-cells in the Tumor

Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor

sCD27

Eotaxin

MIP-1b

sPD-1

Change From Baseline of Selected Cytokines in Peripheral Blood

Overall Study

Symptoms and General Pathology

Disease Progression

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Docetaxel

Antibodies

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Nivolumab will be administered by intravenous infusion over 30 minutes at 240 mg every 2 weeks or at 480 mg every 4 weeks. Sitravatinib capsules will be administered orally, once daily.

Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks.

Nivolumab is an antibody directed at the programmed death receptor-1 (PD-1), blocking its interaction with PD-L1 and PD-L2.

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.

Docetaxel is an anti-neoplastic agent that acts by disrupting the microtubular network in cells.

Ronald L. Shazer, MD, MBA

This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy and checkpoint inhibitor therapy.

Sitravatinib (MGCD516) is an orally-available, small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, TAM (Tyro3, AXL, MERTK) family, VEGFR family, PDGFR family, KIT, FLT3, TRK family, RET, DDR2, and selected EPH family members. Nivolumab is a human IgG monoclonal antibody that binds to the PD-1 receptor and selectively blocks the interaction with its ligands PD-L1 and PD-L2, thereby releasing PD-1 pathway mediated inhibition of the immune response, including anti-tumor immune response. RTKs have been implicated in mediating an immunosuppressive tumor microenvironment, which has emerged as a potential resistance mechanism to checkpoint inhibitor therapy. Inhibition of these RTKs by sitravatinib may augment anti-tumor immune response and improve outcomes by overcoming resistance to checkpoint inhibitor therapy.

Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

A Randomized Phase 3 Study of Sitravatinib in Combination With Nivolumab Versus Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy SAPPHIRE

OS is defined as time from date of randomization to date of death due to any cause

Frequency of patients experiencing treatment-emergent AEs

ORR defined as complete response (CR) or partial response (PR) per RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy

PFS is defined as the time from randomization to the date of the first documentation of objective disease progression or death due to any cause

Bristol-Myers Squibb

Sarcoma

Liposarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms, Adipose Tissue

Soft Tissue Sarcoma

Patients with locally advanced and unresectable or metastatic sarcoma will receive MGCD516 at the discretion of the principal investigator until disease progression, unacceptable toxicity or adverse event(s) or withdrawal of consent.

Administered at 150 mg orally, daily, in continuous 21 day cycles. An orally available, potent small molecular inhibitor of several related receptor tyrosine kinases.

Matthew Ingham, MD

The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.

Sarcomas are a group of cancers which arise from connective tissue and bone, of which more than 50 subtypes exist. Approximately 12,000 people are diagnosed with sarcoma annually in the United States.

Liposarcoma is one of the more common types of soft tissue sarcoma. The primary treatment for liposarcoma is surgery when possible. When liposarcoma is not amenable to surgery, various systemic treatments, including chemotherapy, are used. However, the effectiveness of existing treatments for liposarcoma is limited.

Sitravatinib is an oral, targeted drug which inhibits receptor tyrosine kinases. Receptor tyrosine kinases are proteins on the surface of the liposarcoma cell which play a role in cancer growth. In laboratory work, Sitravatinib effectively suppressed the growth of liposarcoma models. The purpose of this study is to evaluate the safety and efficacy of Sitravatinib in patients with liposarcoma which cannot be removed by surgery.

Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas

A Phase II Trial of Sitravatinib (MGCD516), a Multi-receptor Tyrosine Kinase Inhibitor, in Advanced Liposarcoma and Other Soft Tissue Sarcomas

To assess the efficacy of MGCD516 in patients with advanced liposarcoma by evaluating the progression free rate at 12 weeks as compared historical controls.

To evaluate the safety profile of MGCD516.

To assess the efficacy of MGCD516 in patients with advanced liposarcoma.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer	NCT02219711	Advanced Cancer	MGCD516	18 Years -	Mirati Therapeutics Inc.
Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma	NCT03680521	Clear Cell Rena...	Sitravatinib Nivolumab	18 Years -	Mirati Therapeutics Inc.
Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer	NCT03906071	Metastatic Non-...	Nivolumab Sitravatinib Docetaxel	18 Years -	Mirati Therapeutics Inc.
Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas	NCT02978859	Liposarcoma Metastatic Lipo...	MGCD516	18 Years -	Columbia University
Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer	NCT03906071	Metastatic Non-...	Nivolumab Sitravatinib Docetaxel	18 Years -	Mirati Therapeutics Inc.

Spots Global Cancer Trial Database for mgcd516

Every month we try and update this database with for mgcd516 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mgcd516

Every month we try and update this database with for mgcd516 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mgcd516 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.