Phase 1 Study of IMP321 (Eftilagimod Alpha) Adjuvant to Anti-PD-1 Therapy in Unresectable or Metastatic Melanoma (TACTI-mel)

• ClinicalTrials.gov Identifier: NCT02676869
• Recruitment Status: Completed
• First Posted: February 8, 2016
• Last Update Posted: December 18, 2019
• Sponsor: Immutep Australia Pty. Ltd.
• Information provided by (Responsible Party): Immutep Australia Pty. Ltd.

Study Description

Brief Summary:

The purpose of this study is to determine the safety, tolerability and recommended phase 2 dose of a new drug, known as IMP321, in combination with pembrolizumab when given to patients with unresectable or metastatic melanoma.

Condition or disease	Intervention/treatment	Phase
Stage IV Melanoma; Stage III Melanoma	Drug: IMP321 (eftilagimod alpha); Drug: Pembrolizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Intervention Model: Sequential Assignment
• Intervention Model Description: Study is an open label, dose finding study consisting of 2 parts. In part A, the dose is escalated following the protocol-defined safety observation period of the previous cohort. Patients will receive 9 cycles Pembrolizumab in combination with IMP321. In part B, the dose was defined based on the dose escalation. The treatment duration will be expanded to 19 cycles in the combined treatment.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Open Label, Dose Escalation, Phase 1 Study in Patients With Unresectable or Metastatic Melanoma Receiving IMP321 (LAG-3Ig Fusion Protein-eftilagimod Alpha) as an Adjunctive Therapy to Anti-PD-1 Therapy With Pembrolizumab
• Actual Study Start Date: April 2016
• Actual Primary Completion Date: August 2019
• Actual Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: IMP321 dose escalation; IMP321 administered fortnightly in addition to SOC pembrolizumab.	Drug: IMP321 (eftilagimod alpha); Part A: Single subcutaneous injections of 1 mg (cohort 1), 6 mg (cohort 2) or 30 mg (cohort 3) of IMP321 administered every 2 weeks Part B: Single subcutaneous injections of 30 mg of IMP321 administered every 2 weeks; Other Name: Eftilagimod alpha; Drug: Pembrolizumab; Administered according to the approved label.

Outcome Measures

Primary Outcome Measures :

1. To assess the recommended phase 2 dose [ Time Frame: From the time of inform consent form signature until 30 days after end of treatment ]
2. To asses frequency of adverse events [ Time Frame: From the time of inform consent form signature until 30 days after end of treatment ]
3. To asses severity of adverse events [ Time Frame: From the time of inform consent form signature until 30 days after end of treatment ]
4. To asses duration of adverse events [ Time Frame: From the time of inform consent form signature until 30 days after end of treatment ]

Secondary Outcome Measures :

1. Best overall response rate (ORR) to irRC and RECIST 1.1 [ Time Frame: From the time of inform consent form signature until 30 days after end of treatment. ]
2. Time to next treatment (TTNT) [ Time Frame: Up to 12 months ]
3. Progression-free survival [ Time Frame: Up to 12 months ]
4. Overall survival (part B only) [ Time Frame: Up to 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Main Inclusion Criteria

• Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma
• Currently receiving anti-PD-1 therapy with pembrolizumab and after 3 cycles achieved asymptomatic irPD (slowly progressive, not requiring urgent intervention, and stable performance status) or sub-optimal response (irSD, irPR) as demonstrated in imaging assessments performed within 6 weeks prior to study start
• Female or male 18 years of age or above
• ECOG performance status 0-1
• Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 10. Adequate Laboratory criteria

Main Exclusion Criteria

• More than four prior lines of therapies for advanced or metastatic disease.
• Prior PD-1/PDL-1 targeted therapy
• Currently receiving treatment with another investigational drug, or less than 4 weeks since ending treatment on another investigational drug
• Currently receiving systemic chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (other than pembrolizumab) or less than 4 weeks since completion of these therapies and first dose of study treatment
• History of irAEs from ipilimumab of CTCAE Grade 4 requiring steroid treatment
• Known cerebral or leptomeningeal metastases
• Serious intercurrent infection within 4 weeks prior to first dose of study treatment
• Active acute or chronic infection
• History or evidence of interstitial lung disease or active non-infectious pneumonitis
• Active auto-immune disease requiring immunosuppressive therapy
• HIV positivity, active hepatitis B or hepatitis C
• Continuous systemic treatment with either corticosteroids or other immunosuppressive medications within 4 weeks prior to first dose of study treatment

Contacts and Locations

Locations

Australia, Queensland

Royal Brisbane Womens Hospital

Brisbane, Queensland, Australia, 4029

Princess Alexandra Hospital

Brisbane, Queensland, Australia, 4102

Greenslopes Private Hospital

Brisbane, Queensland, Australia, 4120

Australia, South Australia

Flinders Medical Centre

Adelaide, South Australia, Australia, 5042

Australia, Victoria

Ballarat Hospital

Ballarat, Victoria, Australia, 3353

Alfred Hospital

Melbourne, Victoria, Australia, 3181

Australia, Western Australia

Fiona Stanley Hospital

Perth, Western Australia, Australia, 6150

Sponsors and Collaborators

Immutep Australia Pty. Ltd.

More Information

• Responsible Party: Immutep Australia Pty. Ltd.
• ClinicalTrials.gov Identifier: NCT02676869
• Other Study ID Numbers: IMP321-P012
• First Posted: February 8, 2016
• Last Update Posted: December 18, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action