a phase 1/2a study of imm-1-104 in participants with advanced or metastatic solid tumors

Conditions: Advanced Solid Tumor; Pancreatic Adenocarcinoma; Malignant Melanoma (Cutaneous); Non-small Cell Lung Cancer (NSCLC)

Summary: 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.


Eligibility criteria:
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.

Keywords: pan-ras kras nras hras targeted therapy metastatic cancer advanced cancer ras adenocarcinoma mek dual mek mek 1/2 mitogen-activated protein kinase (mapk) g12a g12c g12d g12f g12r g12s g12v g13c g13d g13r q61h q61k q61l q61r a146t a146v k117n