INFORMING EARLY CLINICAL PROGRAMS WITH EXTERNAL CONTROL ARMS AND TARGET TRIAL EMULATION
Author(s)
Tim Becker, PhD1, Christina Habermehl, PhD2, Athanasios Pallis, MD, MSc, PhD3, Karin Tyroller, PhD4, Samantha Wilkinson, PhD5.
1Merck KGaA, Darmstadt, Germany, 2Merck Healthcare KGaA, Darmstadt, Germany, Germany, Germany, 3Merck SANTE, Lyon, France, 4EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, 5Merck Serono Ltd., Feltham, United Kingdom.
1Merck KGaA, Darmstadt, Germany, 2Merck Healthcare KGaA, Darmstadt, Germany, Germany, Germany, 3Merck SANTE, Lyon, France, 4EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, 5Merck Serono Ltd., Feltham, United Kingdom.
OBJECTIVES: Precemtabart tocentecan (Precem-TcT), an anti-CEACAM5 antibody-drug conjugate with an exatecan (TOP1 inhibitor) payload, has been evaluated in a single-arm clinical study in patients with metastatic colorectal cancer (mCRC). Here, we describe the value of contemporary real-world evidence (RWE) in providing context for interpreting outcomes from single-arm trials during early clinical development.
METHODS: We constructed an external control arm using a target trial emulation framework to benchmark outcomes observed in the Precem-TcT PROCEADE-CRC-01 study (Phase 1; NCT05464030). Real-world data (RWD) were selected from a de-identified, multimodal database of US routine clinical care (Tempus AI, Inc.) and included patients treated with trifluridine/tipiracil plus bevacizumab for mCRC in the majority third-line setting. Confounding was addressed using propensity score matching.
RESULTS: Following target trial emulation, 57 eligible patients receiving trifluridine/tipiracil plus bevacizumab were identified from the real-world setting and propensity score matched to 29 patients treated at the selected Phase 3 dose (2.8 mg/kg Q3W) in the dose-optimisation of PROCEADE-CRC-01. Median progression-free survival (PFS) was 6.9 months (95% CI: 5.6-9.7) in the PROCEADE-CRC-01 cohort after a median follow-up time of 15.2 months versus a PFS of 2.8 months (95% CI: 2.4-4.8) in the RWD cohort. The resulting hazard ratio was 0.45 (95% CI: 0.25-0.80), favouring Precem-TcT.
CONCLUSIONS: RWD comparators are a valuable tool in early-phase oncology development to inform early decision-making for single-arm studies. Using target trial emulation combined with propensity score matching, we constructed a robust standard-of-care comparator arm that is methodologically comparable to the clinical study population. These findings support a favourable PFS profile for Precem-TcT in third-line mCRC and demonstrate the utility of RWE frameworks in generating meaningful comparative evidence during early development to inform early phase decision-making.
METHODS: We constructed an external control arm using a target trial emulation framework to benchmark outcomes observed in the Precem-TcT PROCEADE-CRC-01 study (Phase 1; NCT05464030). Real-world data (RWD) were selected from a de-identified, multimodal database of US routine clinical care (Tempus AI, Inc.) and included patients treated with trifluridine/tipiracil plus bevacizumab for mCRC in the majority third-line setting. Confounding was addressed using propensity score matching.
RESULTS: Following target trial emulation, 57 eligible patients receiving trifluridine/tipiracil plus bevacizumab were identified from the real-world setting and propensity score matched to 29 patients treated at the selected Phase 3 dose (2.8 mg/kg Q3W) in the dose-optimisation of PROCEADE-CRC-01. Median progression-free survival (PFS) was 6.9 months (95% CI: 5.6-9.7) in the PROCEADE-CRC-01 cohort after a median follow-up time of 15.2 months versus a PFS of 2.8 months (95% CI: 2.4-4.8) in the RWD cohort. The resulting hazard ratio was 0.45 (95% CI: 0.25-0.80), favouring Precem-TcT.
CONCLUSIONS: RWD comparators are a valuable tool in early-phase oncology development to inform early decision-making for single-arm studies. Using target trial emulation combined with propensity score matching, we constructed a robust standard-of-care comparator arm that is methodologically comparable to the clinical study population. These findings support a favourable PFS profile for Precem-TcT in third-line mCRC and demonstrate the utility of RWE frameworks in generating meaningful comparative evidence during early development to inform early phase decision-making.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO74
Topic
Clinical Outcomes, Real World Data & Information Systems, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology