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917 Phase 1b trial of first-line bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, plus chemotherapy with or without bevacizumab in cervical cancer
  1. A Oaknin1,
  2. M Gil-Martin2,
  3. E Diver3,
  4. G Jehl4,
  5. SA Gleicher4,
  6. S Chaudhary5,
  7. L Ojalvo5 and
  8. K Hasegawa6
  1. 1Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  2. 2ICO Hospital Duran i Reynals, Barcelona, Spain
  3. 3Stanford Cancer Institute, Stanford, CA, USA
  4. 4Merck KGaA, Darmstadt, Germany
  5. 5EMD Serono Research and Development Institute, Inc., Billerica, MA, USA
  6. 6Saitama Medical University International Medical Center, Hidaki-shi, Saitama-ken, Japan


Introduction/Background*Platinum-containing chemotherapy ± bevacizumab is standard-of-care for recurrent/metastatic/persistent (R/M/P) cervical cancer (CC). Anti-PD-(L)1 therapy has benefit in some patients who progress after first-line (1L) therapy; 1L efficacy is unknown. HPV infection, implicated in >95% of CCs, is linked to TGF-β upregulation. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking PD-L1. Promising activity was observed in patients with recurrent, platinum-experienced CC (response rate 28.2%). We report data from a phase 1b trial evaluating safety of 1L bintrafusp alfa + chemotherapy ± bevacizumab (INTR@PID 046; NCT04551950).

Methodology Patients with R/M/P CC who had not received prior systemic therapy were eligible for cohort 1. They received bintrafusp alfa 2400mg q3w plus cisplatin 50mg/m2 or carboplatin AUC5, paclitaxel 175mg/m2 with (cohort 1A)/without (cohort 1B) bevacizumab 15mg/kg until disease progression, death, unacceptable toxicity, or withdrawal. Primary endpoints: occurrence of predefined dose-limiting toxicities (DLT) ≤4 weeks from treatment start; adverse event occurrence. Target recruitment was 8 patients/cohort, with safety assessments when 3 and 8 patients had completed the DLT period.

Result(s)*As of May 4, 2021, 8 and 9 patients in cohorts 1A and 1B had received therapy for a median of 10.6 and 9.0 weeks. All patients had completed the DLT period and remained on therapy. Two non-bintrafusp alfa-related DLTs were observed in cohort 1B (grade 4 amylase elevation, grade 3 menorrhagia); neither led to treatment discontinuation. Any-grade treatment-related adverse events (TRAEs) occurred in 62.5% and 100% of patients in cohorts 1A and 1B. Grade 3 TRAEs occurred in 3 and 2 patients (cohort 1A: anemia [n=2], lipase increase, decreased neutrophil count, maculo-papular rash [n=1 each]; cohort 1B: anemia, rectal hemorrhage, vaginal bleeding [n=1 each]); 1 patient in cohort 1B had grade 4 anemia. No treatment-related deaths occurred. Preliminary efficacy based on short follow-up showed 3 and 2 tumor responses (2 and 1 pending confirmation) in cohorts 1A and 1B.

Conclusion*No new safety signals were observed with 1L bintrafusp alfa + chemotherapy ± bevacizumab in patients with R/M/P CC. Further studies are warranted.

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