Neoplasms

All Conditions

Heart and Blood Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Thrombosis

Carcinoma, Renal Cell

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

Embolism

Embolism and Thrombosis

Vascular Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenvatinib

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive neoadjuvant lenvatinib (20 mg PO daily) for 12 weeks and pembrolizumab (200 mg IV every 3 weeks for four doses) prior to surgical resection of locally advanced RCC with IVC tumor thrombus. Following surgery, patients will receive adjuvant pembrolizumab (200 mg IV every 3 weeks for up to thirteen doses).

20 mg PO daily for 12 weeks prior to surgery

Neoadjuvant Lenvatinib

200 mg IV every 3 weeks for 4 doses prior to surgery

Neoadjuvant Pembrolizumab

Resection of locally advanced RCC with IVC tumor thrombus

Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection

200 mg IV every 3 weeks for up to 13 doses after surgery

Adjuvant Pembrolizumab

Donna Mitchell

Doreen Simonsen

Vitaly Margulis

Vitaly Margulis, MD

This study will be evaluating safety and efficacy of the combination of lenvatinib and pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell carcinoma with IVC tumor thrombus.

Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus

Safety and Efficacy of Neoadjuvant Lenvatinib and Pembrolizumab in Patients With Renal Cell Carcinoma and IVC Tumor Thrombus

Identify metabolic signatures in plasma that are noninvasive predictors of therapy response and identify metabolic alterations following neoadjuvant therapy in patients who do and do not respond.

Evaluation of changes in size of primary tumor and size and level of IVC tumor thrombus on imaging due to neoadjuvant therapy prior to surgery.

Evaluation of local or metastatic progression on imaging prior to surgery following neoadjuvant therapy.

Assessment of 90 day post-operative safety and morbidity of neoadjuvant therapy by evaluating the incidence of 90 day post-operative grade 3-5 adverse events.

Estimated blood loss in mL during surgery

Operative time in minutes of surgery, length of stay, and intra-operative and post-operative complications

Length of stay of hospital stay for surgery in days, and intra-operative and post-operative complications

Complications that occur in the post-operative period

Evaluation of post-operative survival outcomes including recurrence-free survival and overall survival.

University of Texas Southwestern Medical Center

Professor of Medicine

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Patients will receive neoadjuvant immunotherapy either with anti-PD-1 (pembrolizumab) alone or anti-PD-1 in combination with IDO1 inhibition (epacadostat). Patients will receive Pembrolizumab every 3 weeks over a period of 8 weeks as well as epacadostat starting on day 1 for the duration of pembrolizumab treatment.

All patients will undergo baseline biopsy (mandatory, sampling ≥ 4 areas to represent the tumor), as well as baseline imaging (and for exploratory analysis collection of blood for baseline ctDNA testing and TCR analysis).

Patients will receive pembrolizumab alone or pembrolizumab in combination with epacadostat. Pembrolizumab will be administered at 200 mg IV every 3 weeks for up to 3 doses for no longer than 8 weeks prior to surgery. After surgery, patients will continue pembrolizumab plus epacadostat every 3 weeks for 12 months.

Patients will receive epacadostat in combination with pembrolizumab. Epacadostat will be administered orally at a dose of 100 mg twice a day starting on day 1 for the duration of pembrolizumab treatment. Patients will continue on this combination for no longer than 8 weeks prior to surgery. After surgery, patients will continue pembrolizumab plus epacadostat every 3 weeks for 12 months.

Epacadostat

Tanguy Seiwert, MD

The KEO study is a single arm phase II trial including 44 patients with T1N1-2B, T2N0-N2B head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent resection (+/- adjuvant therapy), who receive neo-adjvuant pembrolizumab + epacadostat.

The primary objective of this study is to determine rate of major treatment effect (MTE) to neoadjuvant pembrolizumab+epacostat immunotherapy in SCCHN compared to historic data with neoadjuvant pembrolizumab alone.

The KEO study is a single arm phase II trial including 44 patients with T1N1-2B, T2N0-N2B head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent resection (+/- adjuvant therapy), who receive neo-adjvuant pembrolizumab + epacadostat. Patients that fit the inclusion criteria (see detailed eligibility criteria below) will receive neoadjuvant immunotherapy either with anti-PD-1 (pembrolizumab) alone or anti-PD-1 in combination with IDO1 inhibition (epacadostat). Patients will receive 200 mg IV Pembrolizumab every 3 weeks for up to 3 doses over a period of 8 weeks as well as oral epacadostat 100 mg BID starting on day 1 for the duration of pembrolizumab treatment.

All patients will undergo baseline biopsy (mandatory, sampling ≥ 4 areas to represent the tumor), as well as baseline imaging (and for exploratory analysis collection of blood for baseline ctDNA testing and TCR analysis). Patients who are unable to safely (or for other reasons unwilling to undergo biopsy at baseline and on treatment 3-4 weeks in for infiltrate assessment are not eligible for the study. MRI is the preferred imaging modality; however, diagnostic CT is acceptable if patient is unable to undergo MRI or as clinically indicated.

Subsequently at week 3-4 an interim assessment will be performed:

1. All patients will undergo imaging with a 2nd MRI scan (or CT, to match prior imaging).
2. All patients will also undergo repeat mandatory on-treatment biopsy consisting of of 4-6 representative samples to compare to the baseline biopsy. Adequacy of response to treatment will be assessed in assessing eradication of tumor/presence of antitumor tumor response (analogous to reports in lung cancer (Forde et al ESMO 2016). The on-treatment biopsy is essential in the assessment of early response and decision to extend neo-adjuvant treatment to 8 weeks is based in large part on this biopsy. In patients where an on-treatment biopsy is not obtained (e.g no longer considered safe or status of patient has changed), patients will automatically be considered non-complete responders, and take off study after 4 weeks (with the very unlikely but possible exceptions of complete response radiologic response at 4 weeks imaging).
3. For exploratory purposes, blood will also be drawn for repeat ctDNA and TCR analysis in order to assess potential suitability of dynamic changes ctDNA or TCR clonality/diversity as candidate biomarkers for follow-up studies.

At the week 3/4 interim assessment, results of the imaging and biopsy will be used to determine response and to determine continuation of immunotherapy induction treatment for up to 8 weeks (full immunotherapy induction course). Patients that demonstrate stable disease or tumor shrinkage radiographically and biopsy demonstrating dense lymphocytic infiltrate with dying tumor / decrease in residual viable tumor will continue on protocol.

Those patients with lack of lymphocytic infiltrate/dying tumor or increasing tumor on radiology (and confirmed on pathology from 2nd biopsy) will be transitioned to standard of care treatment with early salvage surgery or chemoradiation (as clinically indicated).

Pre-surgery assessment: For those patients continuing - a second confirmatory scan will be done 3-4 weeks later again coupled with a blood draw, and followed by surgery at/around week 8 (+/-1 week depending on operating schedules).

Definitive surgery will be done at week 8. Surgical specimens will again be evaluated for percentage residual viable tumor and inflammatory infiltrate. Patients that exhibit complete pathologic response (no viable tumor) will follow close observation with repeat imaging (CT/MRI at 4-6 weeks), clinical exams and a PET scan at 12 weeks post-surgery (as well as serial ctDNA draws (exploratory).

Patients with major pathologic responses (≤10% residual tumor, but tumor present) will be treated with de-escalated adjuvant radiation therapy as determined by the tumor board/radiation oncology.

Patients with a surgical specimen that demonstrates \>10% residual tumor after surgery will undergo standard adjuvant RT/CRT as indicated.

Adjuvant Phase: Patients will continue adjuvant pembrolizumab plus epacadostat every 3 weeks for 12 months and be monitored with ctDNA and imaging.

Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck

Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck (SCCHN): The KEO Trial

MTE will be assessed in the same way as done by Uppaluri et al (Uppaluri ASCO 2017) upon pathologic review and assessment of 50% resolution of tumor with active immune response (termed "major treatment effect" in their study).

Response rate at surgery compared to historic data with chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus	NCT05319015	Renal Cell Carc...	Neoadjuvant Len... Neoadjuvant Pem... Radical nephrec... Adjuvant Pembro...	18 Years -	University of Texas Southwestern Medical Center
Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck	NCT03325465	Squamous Cell C...	Pembrolizumab Epacadostat	18 Years -	University of Chicago

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