Treatment of Advanced or Metastatic Triple-negative Breast Cancer With Adoptive Therapy of PD1+ TILS

Phase 1

Recruiting

• Conditions: Metastatic Triple-Negative Breast Carcinoma
• Interventions: Drug: PD1+ TILs (NUMARZU-001) product infusion

• Registration Number: NCT05451784
• Lead Sponsor: Fundacio Clinic Barcelona

Brief Summary

This is a prospective, multicenter, phase I/II, open-label, two-stage design of PD1+ TILs infusion in metastatic or advanced TNBC. TILS001 includes 3 parts. Previous to each phase inclusion, a specific ICF must be signed by the patient. Participants potentially eligible to participate in the clinical trial will be offered to sign a ICF three times prior to TILs treatment: 1) to allow for collection of archival FFPE tissue samples for determination PD1 by mRNA (Part #1), 2) prior to a fresh metastatic biopsy for selection, isolation and partial expansion of PD1+ TILs (Part #2) and 3) prior to allow for remaining study procedures and TILs therapy (Part #3, Main Consent).

Detailed Description

This trial has been developed in TNBC, a breast cancer subtype with a particularly poor prognosis. The product used for treating participating patients will be selected PD1-positive TILs. Such TILs will be manufactured in Hospital Clinic under the name of NUMARZU-001. The procotol has been designed in three parts to better select participating patients. Molecular pre-screening has been established to select tumors with a higher probability of enrichment by PD1-positive TILs. The pre- screening consists of performing a tumor biopsy and selecting isolation and expansion of PD1- postive TILs to manufacture the final product NUMARZU-001. This part could last almost four weeks, as such patients will continue with the established treatment in the meanwhile. Finally, NUMARZU-001 will be administered if the patient is eligible for part three of the protocol.

Study Timeline

• Study First Submitted: 2022-07-04
• Study First Submitted QC: 2022-07-08
• Study First Posted: 2022-07-11
• Study Start: 2022-07-20
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-24
• Primary Completion: 2025-11-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PD1+ TILs (NUMARZU-001) product infusion	PD1+ TILs (NUMARZU-001) product infusion	The treatment administration is divided in NMA-LD chemotherapy(auxiliary medication), TILs product (IMP) and IL-2 (auxiliary medication).

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	24 weeks from the administration of PD1+ TILS (NUMARZU-001 product)	Overall response rate (ORR) locally determined as the best response (defined as CR and PR) by the investigator according to RECIST 1.1 criteria from the administration of PD1+ TILS (NUMARZU-001 product); on day 0
Incidence of grade 3-5 adverse event (AE)	24 weeks from the administration of PD1+ TILS (NUMARZU-001 product)	Incidence of grade 3-5 adverse event (AE) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, and any grade AE assessed by CTCAE that leads to treatment discontinuation and possibly related to treatment, that occur in the first 24h following PD1+ TILs infusion (prior to IL-2 treatment).; * Incidence of grade 3-5 AEs assessed by the NCI CTCAE version 5.0 taking into account the whole process, which includes NMA-LD chemotherapy followed by TILs infusion and at least one dose of IL-2 treatment.; * All changes in treatment administration including delays, interruptions, reductions or discontinuation and the main reason(s) for these changes.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	24 weeks from the administration of PD1+ TILS (NUMARZU-001 product)	Duration of Response (DoR) defined as the time from the first occurrence of a documented objective response to disease progression, as determined locally by the investigator using RECIST v1.1, or death due to any cause, whichever occurs first.
Overall Survival (OS)	From completion of the Response Assessment Period and up to 5 years from the last study treatment until death, loss to follow-up, or withdrawal of consent	Overall Survival (OS) defined as the time from the administration of PD1+ TILS (NUMARZU-001 product); on day 0 to death due to any cause.
Progression-Free Survival at 6 months(PFS6)	24 weeks from the administration of PD1+ TILS (NUMARZU-001 product)	Progression-Free Survival at 6 months(PFS6) defined as the proportion of patients alive and without progression (as determined locally by the investigator according to Response Evaluation Criteria in Solid Tumor \[RECIST\] 1.1 version) 24 weeks from the administration of PD1+ TILS (NUMARZU-001 product); on day 0
Clinical Benefit Rate at 6 months (CBR6)	24 weeks from the administration of PD1+ TILS (NUMARZU-001 product)	Clinical Benefit Rate at 6 months (CBR6) from the administration of PD1+ TILS (NUMARZU-001 product); on day 0 defined as Complete response (CR), Partial response (PR) or Stable Disease (SD) for at least 6 months, as determined locally by the investigator according to RECIST 1.1 criteria.
Progression-free survival (PFS)	24 weeks from the administration of PD1+ TILS (NUMARZU-001 product)	Progression-free survival (PFS) defined as the timefrom the administration of PD1+ TILS (NUMARZU-001 product); on day 0 to the first occurrence of disease progression, as determined locally by the investigator using RECIST v1.1, or death due to any cause, whichever occurs first.

Trial Locations

Locations (4)

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Clínica universidad de Navarra; 🇪🇸 Pamplona, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain