Immune Therapy in Combination with Checkpoint Inhibitor Treatment

Phase 1

• Conditions: nresectable, Stage III or Stage IV metastatic melanoma who are either previously untreated (cohort A), or whose disease has progressed during PD-1 blockade (cohort B).; MedDRA version: 21.1Level: PTClassification code 10028980Term: NeoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001346-34-GB
• Lead Sponsor: Immodulon Therapeutics Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-19
• Study Completion: 2021-12-02
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Patient must have a histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma excluding uveal/ocular melanoma. Patients with unknown primary melanoma are eligible.
2. Patient has at least one measurable lesion by CT or MRI, according to RECIST 1.1.
3. Patient must have known BRAF V600 mutation status or consent to BRAF V600 mutation testing during the Screening Period.
4. Patients who have had prior radiotherapy must have completed this at least 2 weeks prior to study drug administration (Week 0, Visit 1). Prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to enrolment (Week 0, Visit 1), and all related adverse events have resolved or stabilised.
5. Patient is considered suitable for treatment with nivolumab.
6. Patient provides signed informed consent for participation in the study.
7. Patient has an Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) Performance Status of =1 at Day 0.
8. Patient has Screening laboratory values meeting the following criteria. These should be obtained within 14 days prior to first dose on study:
• Haemoglobin (Hb) =9.0g/dL, absolute neutrophil count =1.5 x 109/L, platelets =100 x 109/L and White Blood Cells (WBC) = 2.0 x 109/L (blood transfusion to achieve these levels are not permitted within 2 weeks of this assessment)
• Total bilirubin =1.5 x upper limit of normal (ULN), excluding cases where elevated bilirubin can be attributed to Gilbert's Syndrome
• Aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT; serum glutamate pyruvate transaminase [SGPT]) each =2.5 x ULN or =5 x ULN in presence of liver metastases
• Creatinine =1.5 x ULN
• Serum albumin =30g/L
9. Patient is aged =18 years.

For cohort A, the following inclusion criteria must also be met for a patient to be eligible to participate in this study:
1. Patient is treatment-naive (i.e. no prior systemic anticancer therapy for unresectable or metastatic melanoma).
2. Patient must have a tumour sample (archived tissue in the last 3 months or newly obtained biopsy) that is adequate for PD-L1 assessment prior to enrolment.

For cohort B, the following inclusion criteria must also be met for a patient to be eligible to participate in this study:
1. Patient is either currently on (or has previously received) treatment with an anti-PD-1 therapy (monotherapy or in combination) for advanced melanoma and has progressive disease by RECIST 1.1 after at least 3 doses of anti-PD-1 given as monotherapy or at least 2 doses of anti-PD-1 given in combination regimes, and has not received any further therapy since for advanced melanoma. The last dose of PD-1 targeted therapy must have been received no more than 12 weeks prior to the start of Screening but more than 6 weeks prior to first IMM-101 administration. For all patients in cohort B, progression must have occurred during the PD-1 targeted treatment and the investigator has deemed it appropriate to continue/start treatment with nivolumab beyond disease progression.
2. Patients must have recovered from any AEs related to prior anti-PD-1 containing regime to Grade 1 or have resolved.
3. Patients with a BRAF mutation must have taken BRAF- and/or MEK-targeted therapy, unless patients are not candidates for, or have refused, these therapies. Anti-PD-1 therapy must be the current or last treatment for advance

Exclusion Criteria

1. Patient has uveal/ocular melanoma. .
2. Patient has active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible for cohort B of the study only, if these have been treated and there is no MRI evidence of progression for at least 8 weeks after treatment is complete and within 21 days prior to first dose of study treatment administration.
3. Patient has previously received treatment with IMM-101.
4. Patient is either receiving concomitant treatment with another investigational product or has received such treatment within the 3 weeks prior to first IMM-101 administration.
5. Patient has any serious or uncontrolled medical disorder or co existing active infection that, in the opinion of the Investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate.
6. Patient has any previous or concurrent malignancy. Patients will not be excluded if they have had adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non melanoma skin cancer, or if previous malignancy was more than 5 years prior to Screening and there are no signs of recurrence.
7. Patient has previously experienced an allergic reaction to any mycobacterial product or any monoclonal antibody.

For cohort A, patients meeting any of the following criteria are also ineligible to participate in this study:
1. Patient has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent.

For cohort B, patients meeting any of the following criteria are also ineligible to participate in this study:
1. Patient has previously experienced an AE related to anti-PD-1 therapy which, in the investigator's opinion, makes them unsuitable for further treatment with nivolumab.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified