Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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.