NCT03323398

Dose Escalation and Efficacy Study of mRNA-2416 for Intratumoral Injection Alone and in Combination With Durvalumab for Participants With Advanced Malignancies

A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Efficacy Study of mRNA-2416, a Lipid Nanoparticle Encapsulated mRNA Encoding Human OX40L, for Intratumoral Injection Alone or in Combination With Durvalumab for Patients With Advanced Malignancies

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 79 (actual)
• Sponsor: ModernaTX, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical study will assess the safety and tolerability of escalating doses of mRNA-2416 alone and in combination with administered fixed doses of durvalumab in participants with relapsed/refractory solid tumor malignancies or lymphoma, as well as the objective response rate (ORR) of mRNA-2416 alone or in combination with durvalumab in ovarian cancer based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The applicable dose of mRNA-2416 will be injected directly into the participant's tumor (intratumoral) and the applicable dose of durvalumab will be administered intravenously.

Detailed description

This is a first-in-human, Phase 1/2, open-label, multicenter, dose escalation and efficacy study designed to determine the safety and tolerability of repeated intratumoral injections of mRNA-2416 alone (Arm A) and in combination with intravenously administered durvalumab (Arm B) in participants with advanced relapsed/refractory solid tumor malignancies or lymphoma and to assess the ORR of mRNA-2416 alone and in combination with durvalumab in ovarian cancer based on RECIST v1.1. The study includes 2 treatment arms (mRNA-2416 monotherapy \[Arm A\],and mRNA-2416 + durvalumab \[Arm B\]), each arm of the study consists of a Dose Escalation period in non-visceral lesions followed by a Dose Confirmation period in visceral lesions and an Expansion period (Arm B only) in participants with ovarian cancer at the MTD/RDE as determined by the Dose Escalation period. Once the expected maximum tolerated dose/recommended dose for expansion (MTD/RDE) has been cleared in Dose Escalation for Arm A, Dose Escalation for Arm B will begin with mRNA-2416 at 1 dose level lower than the Arm A MTD/RDE. Following completion of 6 cycles of mRNA-2416 + durvalumab (Arm B), participants may continue with durvalumab alone until disease progression, unacceptable toxicity, or 24 months of treatment (total), whichever is sooner.

Conditions

• Relapsed/Refractory Solid Tumor Malignancies or Lymphoma
• Ovarian Cancer

Interventions

Type	Name	Description
BIOLOGICAL	mRNA-2416	mRNA encoding human OX40L
BIOLOGICAL	Durvalumab	PD-L1 inhibitor

Timeline

• Start date: 2017-08-15
• Primary completion: 2021-08-18
• Completion: 2021-08-18
• First posted: 2017-10-27
• Last updated: 2024-07-31
• Results posted: 2024-07-31

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study