Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors

Neuroendocrine Tumors Clinical Trial

Official title: A Phase II Study of Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors

Status Recruiting

Clinical Trial Summary

This is the first study to be done in a newly described class of neuroendocrine tumors known as well-differentiated grade 3 neuroendocrine tumors (WD G3 NET). First described in the pancreas in 2017, the classification was broadened to include gastrointestinal tract tumors in 2019. Recent data suggest an equivalent subtype exists in the lungs (NEC with carcinoid morphology). WD G3 NETs can occur de novo as well as the result of grade progression over time. This is a single arm, multi-site, Phase II study in biomarker "unselected" participants. This study will also incorporate serial blood samples, tumor biopsies, and special imaging to better understand the impact of therapy on the tumor and microenvironment. Hyperpolarized (HP) 13C-pyruvate magnetic resonance imaging (MRI) - a novel non-radioactive imaging modality able to provide in vivo measurements of the pyruvate-to-lactate conversion rate (kpl).

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the overall response rate (ORR) of lenvatinib plus pembrolizumab.

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of lenvatinib plus pembrolizumab. II. To evaluate the duration of response (DOR) in patients receiving lenvatinib plus pembrolizumab.

III. To evaluate progression-free survival (PFS) in patients receiving lenvatinib plus pembrolizumab.

EXPLORATORY OBJECTIVES:

I. To evaluate overall survival (OS) in participants receiving lenvatinib plus pembrolizumab.

II. To compare overall response rate (ORR), DOR, and PFS by Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) with the same measures assessed by Response Evaluation Criteria In Solid Tumors version 1.1.

III. To correlate clinical outcomes (ORR, DOR, PFS, OS) with baseline immune cell infiltration, T cell receptor (TCR) repertoires, and programmed death-ligand 1 (PD-L1) staining in pre-treatment biopsies. IV. To assess changes in immune cell infiltration, PD-L1 staining, and TCR repertoires in pre- and post-biopsies.

V. Correlate Ki67proliferative index with outcomes (ORR, DOR, PFS, OS).

IV. To characterize the baseline molecular features (tissue- and blood-based) of G3 NETs treated with lenvatinib and pembrolizumab.

VII. To correlate the molecular features of G3 NET with clinical outcomes (e.g., response/resistance, survival, safety, pharmacodynamic activity) in the setting of treatment with pembrolizumab plus lenvatinib.

VIII. To describe the relationship between baseline tumor growth rate (TGR) and RECIST measurements for all patients.

IX. To examine changes in TGR over time in patients treated with Lenvatinib plus pembrolizumab TGR as assessed by cross-sectional imaging.

X. To investigate the relationship between on-treatment changes in pyruvate-to-lactate conversion rate (kpl) and ORR, PFS, and OS.

XI. To investigate the relationship between baseline tumor proliferative index (as measured by Ki67), metabolic profile (NMR spectroscopy), and pyruvate-to-lactate conversion rate (kpl, as measured by hyperpolarized 13C-pyruvate imaging) and ORR, PFS and OS.

XII. Assessment of baseline heterogeneity of pyruvate-to-lactate conversion rate (kpl) between patients and between tumors within a given participant.

OUTLINE:

There are 2 stages to this study. If at least 2 participants in stage 1 show a demonstrated response, a second stage will open to enroll additional participants. Participants may continue treatment for up to two years of therapy (i.e., 18 doses of pembrolizumab).

After the end of treatment, each participant will be followed for 30 days for adverse event (AE) monitoring. Serious adverse events (SAE) and events of clinical interest (ECI) will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the participant initiates new anticancer therapy, whichever is earlier. Participants who discontinue for reasons other than progressive disease will have post-treatment follow-up for disease status until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. After documented disease progression each participant will be followed by telephone for overall survival and anti-cancer therapy until death, withdrawal of consent, or the end of the study, whichever occurs first. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Neuroendocrine
• High Grade Neuroendocrine Carcinoma, Any Site
• Neuroendocrine Tumors
• Well-Differentiated Neuroendocrine Carcinoma

• NCT number: NCT05746208
• Study type: Interventional
• Source: University of California, San Francisco
• Contact: Phu Lam
• Phone: (415) 353-8337
• Email: Phu.Lam@ucsf.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: July 17, 2023
• Completion date: October 31, 2027