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Developmental therapeutics

3156 - Early FDG-PET Response Correlates With Dose and Clinical Efficacy in Patients With Microsatellite Stable (MSS) Metastatic CRC (mCRC) Treated With the CEA-CD3 T-cell Bispecific Antibody plus Atezolizumab

Date

09 Sep 2017

Session

Developmental therapeutics

Presenters

Federico Sandoval

Citation

Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367

Authors

F. Sandoval1, D. Sabanes Bove2, S. Bouseida3, V. Karanikas4, A. Keelara1, J. Saro4, T. Nayak3

Author affiliations

  • 1 Roche Pharmaceutical Research And Early Development, Roche Innovation Center, CH-4070 - Basel/CH
  • 2 Biostatistics, F. Hoffmann-La Roche Ltd., Basel/CH
  • 3 Roche Pharmaceutical Research And Early Development, Roche Innovation Center, Basel/CH
  • 4 Roche Pharmaceutical Research And Early Development, Roche Innovation Centre, Zurich/CH
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Resources

Abstract 3156

Background

CEA-CD3 TCB (RG7802, RO6958688) is a novel T-cell bispecific antibody targeting CEA on tumor cells and CD3 on T cells. An ongoing phase Ib study (NCT02650713) is exploring the safety, tolerability and efficacy of CEA-CD3 TCB in combination with atezolizumab. We report preliminary results of FDG-PET imaging as an early pharmacodynamic marker for this novel cancer immunotherapy combination in MSS mCRC patients.

Methods

In this study, CEA-CD3 TCB is given QW in combination with atezolizumab 1200 mg Q3W in patients with CEA-expressing solid tumors. As of March 3, 2017, a total of 35 MSS mCRC patients have been treated with CEA-CD3 TCB doses of 5-160 mg; 15 patients were evaluable for PET image analysis. On-treatment FDG-PET scans were performed at week 4 and compared with baseline. On-treatment changes in SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were analyzed in up to 10 measurable lesions per patient, identified at baseline by an independent reviewer. The exploratory statistical analyses used semiparametric Gaussian regression models and Cox PH landmark analyses (for progression-free survival [PFS]).

Results

Early changes in FDG-PET parameters showed a dose-response relationship (MTV: P = 0.0022; TLG: P = 0.0054; SUVmax: P = 0.0081); notably all patients receiving doses ≥ 80 mg (n = 7) showed decreases in SUVmax, TLG and MTV at week 4. Furthermore, week 4 reductions in FDG uptake (MTV: P < 0.001; TLG: P < 0.001; SUVmax: P = 0.0061) correlated with later tumor shrinkage (best change from baseline per RECIST v1.1). Reduction in MTV and TLG, but not SUVmax, correlated with decreases in soluble CEA levels measured at week 6 (MTV: P = 0.013; TLG: P = 0.034; SUVmax: P = 0.54) and longer PFS (MTV: P = 0.013; TLG: P = 0.052; SUVmax: P = 0.85).

Conclusions

In MSS mCRC patients, changes in MTV, TLG and SUVmax correlated with dose and tumor shrinkage. Decreases in 2 FDG parameters (MTV and TLG) correlated with a reduction in soluble CEA levels. Early on-treatment changes in FDG-PET can serve as a pharmacodynamic biomarker related to treatment efficacy.

Clinical trial identification

NCT02650713

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

F. Sandoval, D. Sabanes Bove, S. Bouseida, V. Karanikas, A. Keelara: Roche employee. J. Saro: Employee of Roche and stock holder of Roche. T. Nayak: Roche stock.

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