BO-112 With Pembrolizumab in Unresectable Malignant Melanoma

NCT04570332 | Completed Phase 2 Results DMC

• 3 other identifiers: BOT112-032020-003921-51KEYNOTE-B77 / MK-3475-B77
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 19

Brief Summary

This is a phase 2, single arm, open label, adaptive design study to determine the preliminary anti-tumor activity and confirm the safety of IT BO-112 in combination with intravenous (IV) pembrolizumab. The study will enroll patients with advanced and/or metastatic melanoma that have progressed on anti-PD-1-containing treatment.

Conditions

Melanoma

Keywords

BO112; Intratumoral; Immunotherapy; TLR3; Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Percentage of patients achieving a complete response (CR) or partial response (PR) as best overall response, by independent radiological central review (IRCR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  From the first dose of study treatment to the date of CR or PR assessed up to 2 years

Secondary Outcomes (5)

• Number of Participants With Adverse Events and Serious Adverse Events

  2 years and 9 months

• Disease Control Rate

  From the first dose of study treatment to the date of best response (i.e. CR, PR, or SD) on study up to 2 years

• Duration of Response

  From the date of CR or PR until the date of event or censoring up to 2 years

• Progression Free Survival

  From the first dose of study treatment to the date of radiologic progression or death, whichever comes first, up to 2 years

• Overall Survival

  From the first dose of study treatment to death from any cause up to 2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

Patients will be treated with a combination of IT BO-112 and IV pembrolizumab.BO-112 will be administered once weekly (QW) for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab Q3W will be administered IV. BO-112 will be administered IT at a total dose of 1-2 mg at each administration to 1-8 tumor lesions.

Drug: BO-112 plus pembrolizumab; Procedure: Tissue Biopsies

Interventions

BO-112 plus pembrolizumab DRUG

Patients will be treated with the combination of BO-112 and pembrolizumab. Order of administration should be pembrolizumab then IT BO-112. BO-112 will be administered IT at a total dose of 1-2 mg at each administration to 1-8 tumor lesions using tuberculin (TB) syringes (or equivalent) with 20- to 25-gauge needles

Also known as: KEYTRUDA®

Single Arm

Tissue Biopsies PROCEDURE

Pre and post (if feasible) treatment tumor tissue biopsies will be used for correlative research.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Be willing and able to give written informed consent for the study.
• Be ≥ 18 years of age on day of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed diagnosis of cutaneous or mucosal melanoma.
• Known BRAF status.
• Have unresectable stage III or stage IV melanoma. Patients must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Received at least 6 weeks of standard dosing of an approved anti-PD-1/L1 mAb.
• Demonstrated disease progression (PD) on or after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression.
• Progressive disease documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• i. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
• Anti-PD-1-based therapy should have been the last line of systemic therapy as part of first line treatment. Prior treatment either in neo or adjuvant setting is allowed (if patient did not develop progressive disease while on receiving it). In the case of patients who develop progressive disease during adjuvant therapy, that treatment will be counted as one prior line, and will be eligible if only that prior line has been administered.
• At least one tumoral lesion that is RECIST 1.1 measurable and amenable for IT injection.
• At least one accessible tumor lesion that is amenable to weekly injection. If liver is a site of injection, presence of at least one additional tumor lesion outside the liver amenable for injection.
• Willingness to provide biological samples required for the duration of the study including a fresh tumor biopsy sample. NOTE: If possible, the biopsied lesion should be a non-target lesion.
• Adequate hematologic and organ function defined by the following laboratory results obtained within 2 weeks prior to the first dose of study treatment:

You may not qualify if:

• Uveal melanoma.
• Prior grade 3-4 irAE due to immune checkpoint inhibitors requiring systemic steroids for more than 2 weeks.
• Prior intra-tumoral treatments.
• If a liver lesion is the site of injection:
• macroscopic tumor infiltration by the lesion to be injected into the main portal vein, hepatic vein or vena cava;
• portal vein thrombosis;
• prior embolization of liver lesions;
• radiofrequency, cryotherapy or microwave ablation in the last 6 months;
• Child-Pugh B or C;
• All AST, ALT and bilirubin greater than \>2.5 ULN.
• Contraindications to tumor biopsy and injections of the metastasis(es), such as coagulopathy, therapeutic dose anticoagulant treatment and treatment with long-acting agents such as clopidogrel which cannot be safely stopped.
• Chemotherapy or biological cancer therapy within 4 weeks prior to the first dose of study treatment. Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
• Palliative radiotherapy within 1 week of start of study treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.

Sponsors & Collaborators

• Highlight Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (19)

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, France

Location

Centre Hospitalier Universitaire de Grenoble

Grenoble, France

Location

Hopital Lyon Sud

Lyon, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, France

Location

Centre Hospitalier Universitaire de Nice

Nice, France

Location

Hôpital Ambroise-Paré

Paris, France

Location

Institut Gustave Roussy

Paris, France

Location

H. Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, Spain

Location

H. Universitari Quirón Dexeus

Barcelona, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Clara Campal - HM Sanchinarro

Madrid, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

MD Anderson Cancer Center

Madrid, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

H. General Universitario de Valencia

Valencia, Spain

Location

Related Publications (1)

• Marquez-Rodas I, Dutriaux C, Saiag P, de la Cruz Merino L, Castanon Alvarez E, Robert C, Rodriguez-Moreno JF, Arance A, Cerezuela-Fuentes P, Montaudie H, Sanmamed MF, Gonzalez-Cao M, Charles J, Lopez Criado MP, Berrocal A, de Miguel E, Funck-Brentano E, Prey S, Alamo de la Gala MC, Melero I, Aviles-Izquierdo JA, Roman R, Garcia-Pelaez B, Rodriguez S, Trnkova ZJ, Quintero M, Macia S, Chaney MF, Dalle S. BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203. J Clin Oncol. 2025 Sep;43(25):2806-2815. doi: 10.1200/JCO-24-02595. Epub 2025 Jun 27.

  PMID: 40577656 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

BO-112; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: M. Quintero, CEO
• Organization: Highlight Therapeutics Ltd.

mquintero@highlighttherapeutics.com

+34686219355

Study Officials

• Marisol Quintero, PhD

  Highlight Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a phase 2 study with one single treatment arm (BO-112 in combination with pembrolizumab)

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 30, 2020
• Study Start: December 30, 2020
• Primary Completion: October 3, 2023
• Study Completion: November 4, 2024
• Last Updated: November 26, 2025
• Results First Posted: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12); FR (7)