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

Integr Cancer Ther. 2026 Jan-Dec:25:15347354251410182. doi: 10.1177/15347354251410182. Epub 2026 Feb 13.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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

Trial registration: ClinicalTrials.gov NCT05580172 NCT00689195 NCT04092647.

Keywords: FDG; Withania somnifera; integrative oncology; lung cancer; phase 1 human trial; positron emission tomography.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung* / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Plant Extracts* / adverse effects
  • Plant Extracts* / therapeutic use
  • Plant Leaves / chemistry
  • Positron Emission Tomography Computed Tomography / methods
  • Withania* / chemistry

Substances

  • Plant Extracts
  • Fluorodeoxyglucose F18
  • Biomarkers, Tumor

Associated data

  • ClinicalTrials.gov/NCT05580172
  • ClinicalTrials.gov/NCT00689195
  • ClinicalTrials.gov/NCT04092647