Moffitt logo

Clinical Trials Search

Clinical Trial 19396

Cancer Type: Cutaneous
Interventions:IMO-2125; Ipilimumab; Pembrolizumab (Keytruda); Yervoy (Ipilimumab)

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Joseph Markowitz

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 1/2 Study to Assess the Safety and Efficacy of Intratumoral IMO-2125 in Combination with Ipilimumab or Pembrolizumab in Patients with Metastatic Melanoma

Summary

The goal of this clinical research study is to find the recommended dose of the study drug IMO-2125 that can be given in combination with ipilimumab or in combination with pembrolizumab to patients with metastatic melanoma. Researchers also want to learn if the study drug combination can help to control the disease. The safety of the drug combination will also be studied.

Objective

Primary: The primary objective of Phase 1 is to characterize the safety and determine a recommended Phase 2 dose (RP2D) of IMO-2125 when administered in combination with ipilimumab or when administered in combination with pembrolizumab in patients with metastatic melanoma. The maximum tolerated dose (MTD) and RP2D for IMO-2125 may differ between the combination of IMO-2125 and ipilimumab and the combination of IMO-2125 and pembrolizumab. The primary objective of Phase 2 is to assess preliminary clinical activity of IMO-2125 in combination with ipilimumab or in combination with pembrolizumab at the respective RP2D(s) in patients with metastatic melanoma that is not responsive to PD-1 inhibitor therapy,using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Secondary: The secondary objectives of Phase 1 are to determine the plasma pharmacokinetics (PK) of single-dose IMO-2125 and repeat-dose IMO-2125 PK administered by intratumoral injection in combination with ipilimumab or pembrolizumab. An additional secondary objective of Phase 1 is to describe any preliminary antitumor activity. The secondary objectives of Phase 2 are to further assess the safety and tolerability of IMO-2125 in combination with ipilimumab or in combination with pembrolizumab in patients with metastatic melanoma and to assess treatment response using irRECIST and RECIST v1.1, overall survival (OS), OS at 6 and 12 months, progression-free survival (PFS), PFS at 6 and 12 months, durable response rate (DRR), and duration of response (DoR).

Inclusion Criteria

  • Must have histologically confirmed metastatic melanoma with measurable, stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease.
  • Must have symptomatic or radiographic progression during or after treatment with a PD-(L)1 inhibitor administered either as monotherapy or in combination. 1.) The interval between last PD-(L)1 directed treatment and start of study treatment should be at least 21 days. 2.) Prior BRAF or MEK inhibitor treatment is not required. However, for patients with known BRAF status: Those with BRAF wild type may have had a maximum of two previous systemic regimens for the treatment of melanoma. Those with a BRAF mutation may have had a maximum of three previous systemic regimens for the treatment of melanoma; 3.) Prior ipilimumab is permitted. 4.) Previous treatment with either a PD-1 inhibitor (for patients enrolling on the IMO-2125 + pembrolizumab combination) or CTLA-4 inhibitor (for patients enrolling on the IMO-2125 + ipilimumab combination if applicable) should not have been accompanied by DLT for which permanent discontinuation is recommended (per USPI).
  • Phase 1 participants must have at least two measurable tumor lesions ≥ 1.0 cm that are accessible to biopsy. Phase 2 participants must have at least one measurable lesion (per RECIST v1.1) which may be the same site that is used for the intratumoral injections.
  • ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
  • Adequate hepatic, renal and bone marrow function
  • Women of childbearing potential (WOCBP) and men must agree to use effective contraceptive methods from Screening throughout the study treatment period and until at least 3 months after the last dose of ipilimumab or at least 4 months after the last dose of pembrolizumab.
  • Must have an anticipated life expectancy > 3 months.

  • Exclusion Criteria

  • Potential participants who have received prior therapy with a TLR agonist, excluding topical agents. Patients who have received experimental vaccines or other investigational immune therapies should be discussed with the Medical Monitor to confirm eligibility.
  • Have received systemic treatment with IFN-α within the previous 6 months prior to enrolling into this study.
  • Known hypersensitivity to any oligodeoxynucleotide.
  • Active autoimmune disease requiring disease-modifying therapy.
  • Require concurrent systemic steroid therapy higher than physiologic dose (7.5 mg/day of prednisone).
  • Any form of active primary or secondary immunodeficiency.
  • Another primary malignancy that has not been in remission for at least 3 years.
  • Active systemic infections requiring antibiotics or active hepatitis A, B, or C.
  • Known diagnosis of human immunodeficiency virus (HIV) infection.
  • Previously had a severe reaction to treatment with a human antibody.
  • Known central nervous system, meningeal, or epidural disease.
  • Women who are pregnant or breastfeeding.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Have ocular melanoma.