Combination of Talimogene Laherparepvec With Atezolizumab in Early Breast Cancer

NCT03802604 | Completed Early Phase 1 DMC

• 2 other identifiers: SOLTI-15032018-001300-10
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 4

Brief Summary

PROMETEO is a window opportunity, single arm, exploratory study to evaluate the effect of T- VEC combined with Atezolizumab in women with operable early breast cancer who present residual disease after Neoadjuvant Chemotherapy (NAC). Other eligibility criteria include TNBC or LumB like primary tumor sized at least 1.5 cm, ECOG PS 0-1 and evaluable diagnostic tumor sample.

Conditions

Breast Cancer

Keywords

atezolizumab; T-vec; talimogene laherparepvec

Outcome Measures

Primary Outcomes (1)

• Rate of residual cancer burden class 0 and 1 (RCB0/1)

  As a dichotomous measure of tumor response, RCB 0/1 yes vs. no., after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment.

  24 months since first patient in

Secondary Outcomes (5)

• Rate of pCRB (ypT0/Tis) and pCRBL (ypT0/TisypN0)

  24 months since first patient in

• Tumor ORR

  24 months since first patient in

• Rate of residual cancer burden (RCB)

  24 months since first patient in

• Changes in the expression of a gene signature tracking activated CD8 T-cells.

  24 months since first patient in

• Incidence, duration and severity of AEs assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 4

  24 months since first patient in

Study Arms (1)

Talimogene laherparepvec + Atezolizumab

EXPERIMENTAL

1. Talimogene laherparepvec: Cycle 1 - 10\^6 PFU/mL. Cycle 2, 3, 4 \& 5 - 10\^8 PFU/mL. 2. Atezolizumab 840 mg

Biological: Talimogene laherparepvec; Drug: Atezolizumab

Interventions

Talimogene laherparepvec BIOLOGICAL

Talimogene laherparepvec will be given via intra-tumoral injection at an initial dose of 10\^6 PFU/mL. On week 3 (i.e. 21 days \[± 2\] days), a second talimogene laherparepvec injection will be administered at a dose of 10\^8 PFU/mL. Third, fourth and fifth injections will be administered every 2 weeks (every 14 \[± 2\] days). The maximum volume for each injection will be 4.0 mL.

Also known as: T-VEC, Imlygic

Talimogene laherparepvec + Atezolizumab

Atezolizumab DRUG

Atezolizumab 840 mg will be administered by IV infusion on Day1 week 3, then every 2 weeks (every 14 \[± 2\] days), for a total of 4 treatment courses.

Also known as: Tecentric

Talimogene laherparepvec + Atezolizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Female patients age ≥18 years at the time of informed consent.
• Histologically confirmed diagnosis of non-metastatic primary invasive adenocarcinoma of the breast, with all of the following characteristics:
• TNBC or luminal B-like/HER2-negative breast cancer.
• At least 1 lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by magnetic resonance imaging (MRI).
• Breast cancer eligible for primary surgery
• In the case of a multifocal/multicentric tumor, the largest lesion must be ≥ 15 mm and designated the "target" lesion for all subsequent tumor evaluations.
• ER, PgR and HER2 tumor determination by ASCO/CAP guidelines locally assessed:
• TNBC defined as: ER and PR negative defined as IHC nuclear staining \<1% AND HER2 negative.
• Luminal B-like/HER2 negative defined as:
• ER or PR positive defined as IHC nuclear staining ≥1% AND HER2 negative AND local Ki-67 ≥20% or
• Patient must have injectable and biopsiable disease (direct injection or ultrasound guided).
• Completed ≥ 80% total dose of an anthracycline/taxane-based neoadjuvant regimen recommended by the NCCN guidelines. The addition of carboplatin to a taxane is allowed.
• ECOG Performance Status of 0 or 1.
• Adequate organ function determined within 14 days prior to enrollment, defined as follows:

You may not qualify if:

• Inoperable locally advanced breast cancer after NAC.
• Metastatic (Stage IV) breast cancer.
• Bilateral invasive breast cancer.
• Prior therapy with an anti- PD-1, anti- PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-CTLA- 4 antibody compound, T-VEC or any other oncolytic immunotherapy.
• Prior therapy with tumor vaccine.
• Currently receiving treatment in another investigational device or study drug, or less than 28 days since ending treatment on another investigational device or study drug.
• History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover 10% of body surface. Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
• Active herpetic skin lesions or prior complications of herpetic infection (e.g. herpetic keratitis or encephalitis) and must not require intermittent or chronic treatment with an antiherpetic drug (e.g. acyclovir), other than intermittent topical use.
• Received live vaccine within 28 days prior to enrollment or within 5 months after the last dose of atezolizumab.
• Evidence of clinically significant immunosuppression such as the following:

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Amgen: collaborator
• Roche Pharma AG: collaborator

Study Sites (4)

Hospital Universitari Vall d'Hebrón

Barcelona, Barcelona, 08035, Spain

Location

Centro Integral Oncológico Clara Campal

Madrid, Madrid, 28050, Spain

Location

Hospital Clínico universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Related Publications (1)

• Pascual T, Cejalvo JM, Oliveira M, Vidal M, Vega E, Ganau S, Julve A, Zamora E, Miranda I, Delgado A, Bermejo B, la Cruz-Merino L, Juan M, Ferrero-Cafiero JM, Canes J, Gonzalez X, Villagrasa P, Prat A. SOLTI-1503 PROMETEO TRIAL: combination of talimogene laherparepvec with atezolizumab in early breast cancer. Future Oncol. 2020 Aug;16(24):1801-1813. doi: 10.2217/fon-2020-0246. Epub 2020 Jul 7.

  PMID: 32633563 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

talimogene laherparepvec; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Aleix Prat

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: January 14, 2019
• Study Start: December 10, 2018
• Primary Completion: April 27, 2022
• Study Completion: March 18, 2025
• Last Updated: September 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)