# Phase 1 Trial of Withania somnifera Leaf Extract (RH324) in Advanced Non-Small Cell Lung Cancer Including [18F]FDG PET/CT as a Short-Term Metabolic Biomarker to Assess Efficacy: A Novel Model for Assessment of Complimentary Therapies in Early Phase Human Clinical Trials

## TL;DR

A phase 1 trial tested a leaf extract from Withania somnifera in advanced lung cancer patients, using PET scans to assess its anti-cancer effects and safety.

## Contribution

This study introduces a novel model using FDG-PET/CT as a short-term metabolic biomarker to evaluate complementary therapies in early-phase clinical trials.

## Key findings

- RH324 was safe and well tolerated in advanced NSCLC patients.
- FDG-PET/CT scans showed notable changes in tumor metabolism, supporting RH324's anti-neoplastic effects.
- No new metastatic lesions were identified during the trial.

## Abstract

Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety and tolerability. An exploratory aim was assessment of RH324’s anti-neoplastic effects as measured by changes in tumor metabolism using [18F]-labeled 2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans performed before and after completing a 28-day RH324 monotherapy regimen. A total of 9 patients were enrolled, 5 of which completed the trial, including imaging, and were evaluable.

All study safety and tolerability primary endpoints were met. Analysis revealed notable response rates across different SUV parameters (SUVmax, SUVmean, and SUVpeak) and there were no new metastatic lesions identified, further supporting RH324’s anti-neoplastic effects.

RH324 was safe and well tolerated as a monotherapy in advanced NSCLC. FDG-PET/CT provided a novel methodology as a short-term metabolic endpoint with an in vivo biomarker assessment of potential clinical efficacy using a metabolic surrogate of disease activity. This approach offered deeper insights into tumor metabolism and heterogeneity, underscoring the potential of RH324’s anti-neoplastic effects in treating refractory NSCLC.

ClinicalTrials.gov, Identifier: NCT05580172, Registered on October 17, 2022.