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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05585320
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Immuneering Corporation
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Vinny Hayreh, MD
Principal Investigator Affiliation	Immuneering Corporation
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Advanced Solid Tumor, Pancreatic Adenocarcinoma, Malignant Melanoma (Cutaneous), Non-small Cell Lung Cancer (NSCLC)

Arms & Interventions

Arms

Experimental: IMM-1-104 monotherapy (Treatment Group A)

IMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer

Experimental: IMM-1-104 in combination with mGnP (Treatment Group B)

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

Experimental: IMM-1-104 in combination with mFFX (Treatment Group C)

IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma

Experimental: IMM-1-104 in combination with dabrafenib (Treatment Group D)

IMM-1-104 in combination with dabrafenib for second/third line post-IO melanoma with BRAF mutation

Experimental: IMM-1-104 in combination with pembrolizumab (Treatment Group E)

IMM-1-104 in combination with pembrolizumab for second/third line post-IO melanoma

Interventions

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

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

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

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).

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mayo Clinic, Scottsdale 5313457, Arizona 5551752

Status

Recruiting

Address

Mayo Clinic

Scottsdale 5313457, Arizona 5551752, 85259

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