Different Doses of BI-1607 in Combination With Pembrolizumab and Ipilimumab, in Participants With Unresectable or Metastatic Melanoma

NCT06784648 | Active Not Recruiting Phase 1

• 4 other identifiers: 23-BI-1607-022024-512670-10KEYNOTE-G05MK-3475-G05
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 9

Brief Summary

Why the research is needed: Researchers are looking for a better way to treat melanoma that has spread or cannot be removed surgically. Melanoma is a type of skin cancer that starts in melanocytes, the cells that make the pigment that gives skin its color. In people with cancer, the body cannot control the growth of cells, which can come together to form tumors. This trial's new treatment is called BI-1607. BI-1607 is designed to work by improving the effectiveness of other targeted therapies already used for melanoma treatment; ipilimumab and pembrolizumab. BI-1607 will improve the ability of these two treatments to help the body's defense system to destroy cancer cells.

Conditions

Melanoma Metastatic; Melanoma of Skin; Melanoma BRAF V600E/K Mutated; Melanoma Recurrent; Melanoma Stage III or IV; Melanoma; Melanoma Negative for bRAF; Melanoma Negative for nRAS; Melanomas; Uveal Melanoma, Metastatic

Keywords

anti-CTLA-4; anti-PD-1; resistant anti-PD-1; progressed on treatment with an anti-PD-1/L1; metastatic

Outcome Measures

Primary Outcomes (16)

• Safety and tolerability

  The frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) will be assessed.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  The frequency of dose interruptions, dose modifications and trial intervention discontinuations will be evaluated.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  Changes of body temperature following the infusions will be assessed.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  ECG will be performed and the QTc will be used to assess the cardiac safety.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  Changes in concentrations of hematology laboratory parameters (platlet count, red blood cells count, white blood cells count) will be assessed.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  Changes in blood pressure following the infusions will be assessed.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  Changes in respiration rate following the infusions will be assessed.

  end of Cycle 4 (each cycle is 21 days)

• Safety and tolerability

  Changes in pulse rate following the infusions will be assessed.

  end of Cycle 4 (each cycle is 21 days)

• Recommended doses for the expansion cohort

  During phase 1b, to determine the recommended doses for expansion of BI-1607 and ipilimumab in combination with pembrolizumab.

  End of Cycle 3 (each cycle is 21 days)

• Efficacy

  Phase 2a: The best tumour response rate (according to Response Evaluation Criteria in Solid Tumour (RECIST) v.1.1 and immune RECIST (iRECIST)) will be used to assess the efficacy.

  Through study completion, a maximum of 2 years

• Efficacy

  Phase 2a: The objective response rate (according to Response Evaluation Criteria in Solid Tumour (RECIST) v.1.1 and immune RECIST (iRECIST)) will be used to assess the efficacy.

  Through study completion, a maximum of 2 years

• Efficacy

  Phase 2a: The progression-free survival (PFS) measured in months will be used to assess the efficacy.

  Through study completion, a maximum of 2 years

• Efficacy

  Phase 2a: The time to response measured in months will be used to assess the efficacy.

  Through study completion, a maximum of 2 years

• Efficacy

  Phase 2a: The duration of response (DoR) measured in months will be used to assess the efficacy.

  Through study completion, a maximum of 2 years

• Efficacy

  Phase 2a: The overall survival (OS) measured in months will be used to assess the efficacy.

  Through study completion, a maximum of 2 years

• Safety and tolerability

  Changes in concentrations of clinical chemistry concentrations in blood (haemoglobin, creatinin, albumin, blood urea nitrogen, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, total proteins and phosphate) will be assessed.

  end of Cycle 4 (each cycle is 21 days)

Secondary Outcomes (5)

• Pharmacokinetics profile of BI-1607

  end of Cycle 4 (each cycle is 21 days)

• Pharmacokinetics profile of BI-1607

  end of Cycle 4 (each cycle is 21 days)

• Pharmacokinetics profile of BI-1607

  end of Cycle 4 (each cycle is 21 days)

• Pharmacokinetics profile of BI-1607

  end of Cycle 4 (each cycle is 21 days)

• Immunogenicity of BI-1607 when administered in combination with ipilimumab and pembrolizumab

  end of Cycle 4 (each cycle is 21 days)

Other Outcomes (2)

• Expression levels of Fc receptors, and other immunological and melanoma disease markers

  end of Cycle 4 (each cycle is 21 days)

• Genetic background of participants with respect to FcgR

  First day of treatment

Study Arms (1)

Combination of BI-1607, Ipilimumab and pembrolizumab

EXPERIMENTAL

In each cohort in phase Ib BI-1607 will be given with ipilimumab in 3-week cycles for 4 cycles in combination with pembrolizumab (KEYTRUDA) from cycle 3 for up to 2 years from start of treatment. In the phase 2 pembrolizumab (KEYTRUDA) will be given in combination with BI-1607 and ipilimumab in 3-week cycles for 4 cycles then a pembrolizumab (KEYTRUDA) monotherapy will be provided from cycle 5 for up to 2 years from start of treatment.

Biological: pembrolizumab (KEYTRUDA®); Biological: BI-1607; Biological: Ipilimumab (YervoyTM, 50 mg/10 mL solution)

Interventions

pembrolizumab (KEYTRUDA®) BIOLOGICAL

fixed dose 200mg

Combination of BI-1607, Ipilimumab and pembrolizumab

BI-1607 BIOLOGICAL

Each cohorts will receive either 350mg or 700mg per cycle for 4 cycles

Combination of BI-1607, Ipilimumab and pembrolizumab

Ipilimumab (YervoyTM, 50 mg/10 mL solution) BIOLOGICAL

Each cohort will receive either 1mg/kg or 3mg/kg for 4 cycles

Combination of BI-1607, Ipilimumab and pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Is willing and able to provide written informed consent for the trial.
• Is ≥ 18 years of age on the day of signing informed consent.
• Has histologically confirmed advanced melanoma (unresectable or metastatic melanoma) with established disease progression.
• Participants must have progressed on treatment with an anti-PD-1/L1 mAb. Subjects with uveal melanoma are not required to have received any prior anti-PD-1/L1 treatment. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti PD-1/L1 as defined by RECIST v1.1.
• The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented disease progression, in the absence of rapid clinical progression.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• Participants may have received previous treatment with BRAF inhibitors alone or in combination with mitogen extracellular kinase (MEK) inhibitors.
• Has at least 1 measurable disease lesion as defined by RECIST v1.1 criteria.
• Must be willing to provide tumour biopsies as specified in the schedule of assessments (SoA) unless otherwise discussed and agreed with the Sponsor in case a biopsy cannot be taken for a medical/safety reason.
• Has a life expectancy of ≥ 12 weeks.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function as confirmed by laboratory values
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrolment.

You may not qualify if:

• Has previously been treated with an anti-CTLA-4 mAb or anti-LAG3 mAb (anti-Lymphocyte Activation Gene 3).
• Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
• Has received the following:
• Chemotherapy or small molecule products within 4 weeks of first dose of BI-1607.
• Radiotherapy within 2 weeks of first dose of BI-1607, or has radiation-related toxicities, requiring corticosteroids. Participants who have previously had radiation pneumonitis are not allowed.
• Immunotherapy or biological anti-cancer therapy or an investigational agent or an investigational device within 4 weeks prior to the first dose of BI-1607.
• Has not recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline.
• Has had major surgery from which the participant has not yet recovered or is scheduled to have major surgery \< 28 days prior to the first dose of trial intervention.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.
• Is participating or planning to participate in another interventional clinical trial or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to first dose of trial intervention.
• Has history of allogeneic tissue/solid organ transplant.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial intervention .
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.

Sponsors & Collaborators

• BioInvent International AB: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (9)

Charité - Universitatsmedizin Berlin

Berlin, Germany

Location

University Hospital Essen

Essen, Germany

Location

University Hospital Heidelberg

Heidelberg, Germany

Location

University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg and Clinical Cooperation Unit Dermato-Oncology(G300) German Cancer Research Center(DKFZ)

Mannheim, Germany

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

University Hospital 12 de Octubre

Madrid, Spain

Location

Sarah Cannon Research Institute UK

London, Greater London, W1G 6AD, United Kingdom

Location

Velindre Cancer Centre

Cardiff, Wales, CF14 2TL, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma; Neoplasm Metastasis

Interventions

pembrolizumab; Ipilimumab; Solutions

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; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations

Study Design

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

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: January 20, 2025
• Study Start: December 11, 2024
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 1 year after the last patient last visit.
• Access Criteria: Abbreviated CSR published online

Locations

GB (3); DE (4); ES (2)