Symptoms and General Pathology

All Conditions

Neoplasms

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

Adenocarcinoma, Follicular

Leukemia-Lymphoma, Adult T-Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neoplasms, Squamous Cell

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Adult T-cell Leukemia/lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive lenvatinib PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.

Laboratory Biomarker Analysis

Lenvatinib Mesylate

Bryan R Haugen

This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with differentiated thyroid cancer that has spread to other places in the body or has come back and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To investigate the clinical efficacy, as indicated by the rate of complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, of combination therapy with pembrolizumab and lenvatinib in lenvatinib-naive patients with progressive radioiodine-refractory differentiated thyroid cancers (DTC). (Cohort 1) II. To determine the overall response rate (ORR) by the addition of pembrolizumab to patients with radioiodine-refractory DTC who have progressive disease on lenvatinib alone. (Cohort 2)

SECONDARY OBJECTIVES:

I. To determine the safety profile and toxicity of combination therapy with pembrolizumab and lenvatinib in patients with progressive DTC. (Cohort 1 and cohort 2) II. To determine progression-free survival (PFS) and overall survival (OS). (Cohort 1 and cohort 2)

CORRELATIVE RESEARCH OBJECTIVES:

I. To correlate tumor response (RECIST 1.1) with pretreatment frequency of CD8+ T cells in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) II. To correlate tumor response (RECIST 1.1) with pretreatment PD-L1 and PD-L2 levels in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) III. To correlate tumor response (RECIST 1.1) with pretreatment frequency of lymphocytes expressing CD3, CD4, PD-1, FoxP3, or CD20, and of CD163+ macrophages. (Cohort 1 and cohort 2) IV. To correlate tumor response (RECIST 1.1) with the phenotype and frequency of key leukocyte subsets (i.e., PD-1+ T cells, regulatory T cells \[Tregs\], myeloid subsets) in the peripheral blood before, at 6 and 18 weeks on therapy, and at 54 weeks (study completion), progressive disease (PD), or study withdrawal. (Cohort 1) V. To correlate tumor response (RECIST 1.1) with PD-1+ T cell functional capacity. (Cohort 1) VI. To correlate tumor response (RECIST 1.1) with serum anti-thyroglobulin antibody levels assessed before, and at 18 weeks on therapy. (Cohort 1 and 2) VII. To correlate tumor response (RECIST 1.1) with tumor mutation status. (Cohort 1) VIII. To broadly investigate mechanisms of response and resistance to combination therapy, gene expression profiles will be generated from frozen biopsies for analysis by ribonucleic acid-sequencing (RNA-Seq). (Cohort 1)

OUTLINE:

Patients receive lenvatinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.

After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)

Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers: A Phase II Study

All analyses with respect to the translational component of this study are intended to be hypothesis-generating and descriptive in manner. Clinical data (i.e. CR rates confirmed response rates, PFS, OS, etc.) will be correlated with tumor marker data of interest (CD8+, PD-L1, PD-L2, T cell functional capacity markers, anti-thyroglobulin antibody levels, tumor mutation status, and other markers). The Chi-Square (or Fisher's Exact test) will be used to assess the association of categorical clinical data with categorical biomarker data. Time-to-event clinical data (PFS, OS) will be correlated with biomarker data using Kaplan-Meier methodology and Cox regression models. Logistic regression models will also be used to predict binary clinical data with baseline biomarker data. Finally, graphical methods and descriptive statistics will be used to summarize the data as well. Two-sided p-values \< 0.05 will be considered statistically significant.

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will use a one-stage binomial design.

Assessed by RECIST 1.1. Will use a 2-stage Simon Optimal MinMax design.

Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. All patients that have initiated treatment will be considered evaluable for assessing adverse events. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. Only the grade 2+ adverse events will be assessed, regardless of relationship to the study treatment.

The distribution of PFS will be estimated using the method of Kaplan-Meier.

The distribution of survival at 12 months will be estimated using the method of Kaplan-Meier.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

All patients that began treatment were assessed for adverse events

Cohort 1

Cohort 2

Lenvatinib-naïve patients\> Patients receive lenvatinib 20mg PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.\> \> Laboratory Biomarker Analysis: Correlative studies\>

\> Lenvatinib: Given PO\>

\> Lenvatinib Mesylate: Given PO\>

\> Pembrolizumab: Given IV

Previously progressed on Lenvatinib alone\> Patients receive lenvatinib daily dose at progression QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.\> \> Laboratory Biomarker Analysis: Correlative studies\>

\> Lenvatinib: Given PO\>

\> Lenvatinib Mesylate: Given PO\>

\> Pembrolizumab: Given IV

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Prior systemic VEGFR-active kinase inhibitor therapy

Histologic subtype of primary tumor

ECOG Performance Status

All enrolled patients were included in baseline analysis

Bryan Haugen, M.D.

All evaluable patients in cohort 1 were analyzed for this endpoint.

Complete Response Rate (Cohort 1)

All evaluable patients in cohort 2 were analyzed for this endpoint.

Confirmed Response Rate (Cohort 2)

Lenvatinib-naïve patients

\> Patients receive lenvatinib 20mg PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.

\>

\> Laboratory Biomarker Analysis: Correlative studies

\>

\> Lenvatinib: Given PO

\>

\> Lenvatinib Mesylate: Given PO

\>

\> Pembrolizumab: Given IV

Previously progressed on Lenvatinib alone

\> Patients receive lenvatinib daily dose at progression QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.

\>

\> Laboratory Biomarker Analysis: Correlative studies

\>

\> Lenvatinib: Given PO

\>

\> Lenvatinib Mesylate: Given PO

\>

\> Pembrolizumab: Given IV

All evaluable patients were analyzed for this endpoint.

Number of Patients Experiencing Grade 3+ Adverse Events

Progression Free Survival (PFS)

Overall Survival (OS)

Biomarker Levels Analysis Following Pembrolizumab and Lenvatinib Combination Therapy

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Infections

Digestive System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Breast Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Communicable Diseases

Melanoma

Carcinoma, Renal Cell

Acquired Immunodeficiency Syndrome

HIV Infections

Small Cell Lung Carcinoma

Carcinoma, Transitional Cell

Sarcoma

Melanoma, Cutaneous Malignant

Sarcoma, Kaposi

Carcinoma, Small Cell

Carcinoma, Medullary

Syndrome

Immunologic Deficiency Syndromes

Skin Neoplasms

Carcinoma, Neuroendocrine

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Neoplasms, Connective and Soft Tissue

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

Virus Diseases

RNA Virus Infections

Slow Virus Diseases

Kidney Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Herpesviridae Infections

DNA Virus Infections

Neoplasms, Vascular Tissue

Carcinoma, Bronchogenic

Bronchial Neoplasms

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Small Cell Lung Cancer

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Soft Tissue Sarcoma

Kaposi Sarcoma

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Nivolumab

Patients receive cabozantinib s-malate PO QD on days 1-28 of each cycle and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 1 year or 1 year after a partial response is achieved, or 6 months after a complete response is achieved in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT scan and/or MRI as well as blood sample collection throughout the trial.

Biospecimen Collection

Cabozantinib S-malate

Computed Tomography

Magnetic Resonance Imaging

Haiying Cheng

This phase I trial investigates the side effects of cabozantinib and nivolumab in treating patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who are undergoing treatment for human immunodeficiency virus (HIV). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may shrink or stabilize cancer in patients undergoing treatment for HIV.

PRIMARY OBJECTIVES:

I. To determine the safety of combined nivolumab and cabozantinib s-malate (XL184 \[cabozantinib\]) in human immunodeficiency virus (HIV) patients with advanced solid tumors.

II. To determine the feasibility to deliver the combined nivolumab and XL184 (cabozantinib) for a minimum of 4 cycles in at least 75% of the subjects in the expanded cohort with Kaposi sarcoma (KS) or to achieve a confirmed objective response.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity in subjects with Kaposi sarcoma (KS).

II. To assess the effect of treatment on participants' immune status (CD4 and CD8 cell counts) and HIV viral loads.

III. To preliminarily evaluate the objective response rate (ORR) to the combination treatment in subjects with KS.

EXPLORATORY OBJECTIVES:

I. To assess duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in subjects with KS.

II. To assess the PD-L1 immunohistochemistry (IHC) status in tumors and tumor microenvironment and its association with clinical outcome.

III. To assess the expression characteristics and cellular distribution of immune checkpoints (PD-L1, B7x, HHLA2, B7H3), infiltrating immune cells (CD4 T cells, CD8 T cells, regulatory T-cells \[Treg\], myeloid-derived suppressor cell \[MDSC\]), and other tumor microenvironment biomarkers (VEGF, VEGFR, MET, and AXL) in the tissue by multiplex quantitative immunofluorescence (MQIF).

IV. To correlate markers of immune activation and expansion of immune cell subsets and cytokines with clinical outcomes.

V. To assess the treatment effects on latent HIV reservoir. VI. To investigate the dynamic changes of immune checkpoints, angiogenesis markers, and infiltrating immune cells among subjects with available pre- and post-treatment biopsy samples (including subjects with Kaposi sarcoma \[KS\]).

OUTLINE:

Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28 of each cycle and nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 1 year or 1 year after a partial response is achieved, or 6 months after a complete response is achieved in the absence of disease progression or unacceptable toxicity. Patients also undergo a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as blood sample collection throughout the trial.

After completion of study treatment, patients are followed up for 16 weeks.

Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV

Pilot Trial of Nivolumab Plus Cabozantinib for Advanced Solid Tumors in Patients With HIV Infection

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Change in serum markers of immune activation- immune cell subsets and cytokine levels at each time point from baseline will be analyzed using paired nonparametric Wilcoxon sign-rank tests or paired t-tests in exploratory analyses. Will correlate markers of immune activation and expansion of immune cell subsets and cytokines with clinical outcome.

Changes in immune checkpoint (PD-L1, B7x, B7-H3, HHLA2) markers at each time point from baseline will be analyzed using paired nonparametric Wilcoxon sign-rank tests or paired t-tests in exploratory analyses.

Changes in angiogenesis markers at each time point from baseline will be analyzed using paired nonparametric Wilcoxon sign-rank tests or paired t-tests in exploratory analyses.

Changes in infiltrating immune cell markers at each time point from baseline will be analyzed using paired nonparametric Wilcoxon sign-rank tests or paired t-tests in exploratory analyses.

DLTs will be defined during cycle 1 of therapy.

Will assess immune status (CD4 and CD8 cell counts). Changes in immune status at each time point from baseline will be analyzed using paired non-parametric Wilcoxon sign-rank tests or paired t-tests in exploratory analyses.

Will assess HIV viral loads. Changes in viral loads at each time point from baseline will be analyzed using paired nonparametric Wilcoxon sign-rank tests or paired t-tests in exploratory analyses.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)	NCT02973997	Columnar Cell V... Follicular Vari... Metastatic Thyr... Metastatic Thyr... Poorly Differen... Recurrent Diffe... Recurrent Thyro... Recurrent Thyro... Stage III Diffe... Stage III Thyro... Stage III Thyro... Stage IV Thyroi... Stage IV Thyroi... Stage IVA Diffe... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Diffe... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Diffe... Stage IVC Thyro... Stage IVC Thyro... Tall Cell Varia... Thyroid Gland H... Unresectable Di... Unresectable Th...	Laboratory Biom... Lenvatinib Lenvatinib Mesy... Pembrolizumab	18 Years -	Academic and Community Cancer Research United
Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV	NCT04514484	Advanced Differ... Advanced Head a... Advanced Hepato... Advanced Kaposi... Advanced Lung N... Advanced Lung S... Advanced Malign... Advanced Melano... Advanced Ovaria... Advanced Prosta... Advanced Renal ... Advanced Thyroi... Advanced Triple... Advanced Urothe... Anatomic Stage ... Anatomic Stage ... Castration-Resi... Clinical Stage ... Clinical Stage ... HIV Infection Metastatic Diff... Metastatic Head... Metastatic Hepa... Metastatic Kapo... Metastatic Lung... Metastatic Lung... Metastatic Mali... Metastatic Mela... Metastatic Ovar... Metastatic Pros... Metastatic Rena... Metastatic Thyr... Metastatic Trip... Metastatic Urot... Recurrent Diffe... Recurrent Head ... Recurrent Hepat... Recurrent Kapos... Recurrent Lung ... Recurrent Lung ... Recurrent Malig... Recurrent Melan... Recurrent Ovari... Recurrent Prost... Recurrent Renal... Recurrent Thyro... Recurrent Tripl... Recurrent Uroth... Refractory Diff... Stage III Diffe... Stage III Hepat... Stage III Lung ... Stage III Ovari... Stage III Prost... Stage III Renal... Stage III Thyro... Stage IV Differ... Stage IV Hepato... Stage IV Lung C... Stage IV Ovaria... Stage IV Prosta... Stage IV Renal ... Stage IV Thyroi...	Biospecimen Col... Cabozantinib S-... Computed Tomogr... Magnetic Resona... Nivolumab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recurrent differentiated thyroid gland carcinoma