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

Brief summary public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: IMM-1-104 Monotherapy (Treatment Group A). Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met

Intervention public domain (ClinicalTrials.gov)

Drug: IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B). Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of gemcitabine and nab-paclitaxel until treatment discontinuation criteria are met. Gemcitabine will be administered at a dose of 1000 mg/m\^2 nab-Paclitaxel will be administered at a dose of 125 mg/m\^2

Intervention public domain (ClinicalTrials.gov)

Drug: IMM-1-104 + modified FOLFIRINOX (Treatment Group C). Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of modified FOLFIRNOX until treatment discontinuation criteria are met. FOLFIRINOX will be administered as follows: Folinic Acid will be administered at 400 mg/m\^2 Fluorouracil will be administered at 2400 mg/m\^2 Irinotecan will be administered at 150 mg/m\^2 Oxaliplatin will be administered at 85 mg/m\^2

Intervention public domain (ClinicalTrials.gov)

Drug: IMM-1-104 + dabrafenib (Treatment Group D). Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with twice daily oral dose of dabrafenib until treatment discontinuation criteria are met. Dabrafenib will be administered at a dose of 150mg daily (75mg twice daily).

Intervention public domain (ClinicalTrials.gov)

Drug: IMM-1-104 + pembrolizumab (Treatment Group E). Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of pembrolizumab in sequence or concurrently depending on the enrolled cohort (two sub cohorts) until treatment discontinuation criteria are met. Pembrolizumab will be administered at a dose of 400mg.

Arm public domain (ClinicalTrials.gov)

IMM-1-104 monotherapy (Treatment Group A) (experimental): IMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer

Arm public domain (ClinicalTrials.gov)

IMM-1-104 in combination with mGnP (Treatment Group B) (experimental): IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma

Arm public domain (ClinicalTrials.gov)

IMM-1-104 in combination with mFFX (Treatment Group C) (experimental): IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma

Arm public domain (ClinicalTrials.gov)

IMM-1-104 in combination with dabrafenib (Treatment Group D) (experimental): IMM-1-104 in combination with dabrafenib for second/third line post-IO melanoma with BRAF mutation

Arm public domain (ClinicalTrials.gov)

IMM-1-104 in combination with pembrolizumab (Treatment Group E) (experimental): IMM-1-104 in combination with pembrolizumab for second/third line post-IO melanoma

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Adverse Events. Number of participants with adverse events Time frame: From treatment initiation through 30 days following the last IMM-1-104 dose.

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Dose-Limiting Toxicities. Number of participants with dose-limiting toxicities Time frame: The first 21 days of study treatment.

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Recommended Phase 2 Candidate Optimal Dose. Selection of candidate optimal dose to take forward into Ph2a Time frame: Initiation of study treatment through 21 days (up to approximately 18 months).

Primary outcome public domain (ClinicalTrials.gov)

Phase 2a: Overall Response Rate. The proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria Time frame: After up to 48 weeks (12 cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104. Time frame: After 12 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104. Time frame: After 12 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104. Time frame: After 12 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Disease Control Rate (DCR). Time frame: After 16 weeks (4 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Progression Free Survival (PFS). Time frame: Up to approximately 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Duration of Response (DOR). Time frame: Up to approximately 2 years..

Eligibility public domain (ClinicalTrials.gov)

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 …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 209 participants (actual).