A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors

A Phase 1/2a, Open-Label, Multicenter, Nonrandomized, Safety and Anti-tumor Activity Study of IMM-1-104, a Novel Oral Dual MEK1/2 Inhibitor in Participants With Advanced or Metastatic Solid Tumors

This is an open-label, dose-exploration and expansion study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of IMM-1-104 when administered as monotherapy or in combination with approved agents in participants with RAS-mutated or RAS/MAPK activated advanced or metastatic solid tumors. The dose exploration will identify the candidate recommended Phase 2 candidate optimal dose of IMM-1-104 to further explore the anti-tumor activity of IMM-1-104 as monotherapy and in combination with approved agents in multiple Phase 2a proof-of-concept cohorts in malignancies of interest.

Inclusion Criteria:

• Must be ≥18 years of age

• Must have histologically or cytologically confirmed diagnosis as follows:

  1. Monotherapy Phase 1: A locally advanced unresectable or metastatic solid tumor malignancy that harbors a RAS (KRAS, NRAS, or HRAS) activating mutation.
  2. Monotherapy Phase 2a: A locally advanced unresectable or metastatic solid tumor malignancies: pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, or RAS-mutant non-small cell lung cancer (NSCLC)
  3. Combination therapy (both phases): A locally advanced unresectable or metastatic PDAC
  4. Combination therapy Phase 2a, Treatment D: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma with BRAF mutation. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
  5. Combination therapy Phase 2a, Treatment E: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.

• Participants must be treatment naive or received prior systemic standard-of-care treatment as follows:

  1. Monotherapy Phase 1: received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease

  2. Monotherapy Phase 2a:

     1. First-line PDAC participants will have received no previous systemic anti-cancer therapy. Second-line PDAC participants will have received no more than one prior systemic anti-cancer therapy.
     2. First-line melanoma participants will have received no previous systemic anti-cancer therapy. Second- and third-line participants will have received and failed one or two prior systemic anti-cancer therapies, respectively.
     3. NSCLC participants will have received at least one and no more than two previous lines of systemic therapy.

  3. Combination therapy (both phases): PDAC participants will have received no previous systemic anti-cancer therapy for their advanced or metastatic disease.

• Must have evidence of measurable disease (at least one target lesion) per RECIST v1.1 criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate organ function

Exclusion Criteria:

• Inability to swallow oral medications
• Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases
• History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of serous retinopathy, retinal edema, or retinal pigment epithelial detachment (RPED)
• Impaired cardiovascular function or clinically significant cardiac disease
• History of rhabdomyolysis within 3 months prior to start of study treatment
• Active skin disorder requiring systemic treatment within 3 months prior to the start of study treatment
• Participants with active, uncontrolled autoimmune disease or participants actively being treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors for management of their autoimmune disease are excluded
• Receipt of an allogeneic tissue/solid organ transplant
• Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.