Study Assessing MTD, Safety, Tolerability, PK and Anti-tumor Effects of LNS8801alone and With Pembrolizumab

Prescreening for genotyping: 1. Has histopathologically confirmed locally advanced or metastatic solid tumor cancer. 2. Is able to understand and voluntarily sign a written informed consent form and is willing and able to comply with protocol requirements. 3. Is considered likely to meet the detailed inclusion and

for treatment when required. Inclusion Criteria for treatment portion of study: 1. Has histopathologically confirmed locally advanced or metastatic solid tumor cancer (or lymphoma in Phase 1). The solid tumor cancer is further defined in some cohorts as: 1. Phase 1B monotherapy expansion cohort: Has melanoma, except uveal melanoma, and has previously received anti-PD-1/L1 therapy and is now not eligible for anti-PD-1 treatment in the judgement of the Investigator due to prior severe immune related adverse events, and has not received intervening cancer therapy since the anti-PD-1/L1 therapy. 2. Monotherapy Cohort M2: Has pancreatic, gastric, non small cell lung cancer (NSCLC), or colorectal cancer. 3. Monotherapy Cohort M3: Has cutaneous melanoma, and has previously received anti-PD-1/L1 therapy and is now not eligible for anti-PD-1 treatment in the judgement of the Investigator due to prior severe immune related adverse events, and has not received intervening cancer therapy since the anti-PD-1/L1 therapy. 4. Monotherapy Cohort M4: Has any solid tumor malignancy, except cutaneous melanoma, and has previously received anti-PD-1/L1 therapy and is now not eligible for anti-PD-1 treatment in the judgement of the Investigator due to prior severe immune related adverse events, and has not received intervening cancer therapy since the anti-PD-1/L1 therapy. 5. Monotherapy Cohort M5: Has metastatic uveal melanoma, and has received ≤ 2 prior lines of prior systemic therapy. 6. Phase 1B combination expansion cohort: Has any locally advanced or metastatic solid tumor cancer, and has first had a clinical benefit from, followed by documented disease progression on an anti-PD-1/L1 treatment administered either as monotherapy or in combination. Clinical benefit is defined as a complete or partial response of any duration or stable disease for at least 16 weeks with at least one scan showing stable disease. Patients should not have received intervening therapy that did not include anti-PD1/L1 between finishing anti-PD-1/L1 treatment and commencing study treatment. Disease progression on an anti-PD-1/L1 therapy is defined as both: 1. Having received anti-PD-1/L1 therapy at least twice if dosed every 4 weeks (q4w) or longer, at least 3 times if dosed every 3 weeks (q3w), or at least 4 times if dosed every 2 weeks (q2w) and, 2. Having documented clinical or radiographic progression of disease (PD) while on anti-PD-1/L1 therapy. 7. Combination Therapy Cohort C2: Has pancreatic, gastric, NSCLC, or colorectal cancer. 8. Combination Therapy Cohort C3: Has metastatic NSCLC expressing PD-L1 with a Tumor Proportion Score (TPS) ≥1% and ≤49% as determined by an FDA-approved test, and must not have EGFR or ALK genomic tumor aberrations or have demonstrated disease response on or following FDA-approved therapy for these aberrations, and is PD-1/L1 naïve, and is eligible for pembrolizumab as the standard of care or has no available standard of care. 9. Combination Therapy Cohort C5: Has metastatic uveal melanoma and, has received ≤ 2 prior lines of prior systemic therapy. 10. Combination Therapy Cohort C6: Has cutaneous melanoma. 2. Has no standard of care or the patient declines standard of care options. a. An exception to this is metastatic NSCLC patients expressing PD-L1 with a Tumor Proportion Score (TPS) ≥1% and ≤49% who may enter Phase 2 pembrolizumab Combination Therapy Cohort C3 with anti-PD-1 therapy as their standard of care. 3. Has measurable disease per RECIST v1.1 or RANO as assessed by the local site investigator/radiologist. Lesions in a previously irradiated area are measurable if progression has been demonstrated after radiation. Lesions must be measurable in at least 2 dimensions in a spiral CT scan or MRI. For lymphoma patients only, the minimum measurement must be \>15 mm on the long axis and \>10 mm on the short axis. a. Patients with RECIST target lesions in bones must have a PET scan between their last cancer therapy and Cycle 1 Day 1. 4. Be at least18 years of age on day of signing informed consent. 5. Have an Eastern Cooperative Oncology Group Performance Status of 0 or 1. 6. Have an estimated life expectancy of \>3 months. 7. Patients who have surgically accessible lesions should agree to biopsies from nonirradiated tumor lesions or irradiated tumor lesions that have shown progression since irradiation. For the avoidance of doubt, if no surgically accessible lesions exist or a biopsy is contraindicated, patients may still enter the study. 8. Be able to swallow capsules and tablets. 9. Have adequate organ and bone marrow function defined by: 1. Absolute neutrophil count \>=1.5 × 109/L (\>=1500/mm3). 2. Hemoglobin \>=9.0 g/dL or equivalent. Criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Participants can be on a stable dose of erythropoietin (≥ 3 months). 3. Platelet count \>=75 × 10e9/L (\>=75,000/mm3) for LNS8801 monotherapy cohorts Platelet count \>=100 × 10e9/L (\>=100,000/mm3) for LNS8801/pembrolizumab combination cohorts. 4. Total bilirubin \<=1.5 × institutional upper limit of normal (ULN), unless known Gilbert syndrome has been diagnosed. 5. Measured or calculated creatinine clearance (glomerular filtration rate) \>=50 mL/min/1.73 m2. 6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<=2.5 × ULN or \<=5 × ULN with cancer in the liver. 7. For cohorts receiving LNS8801/pembrolizumab combination therapy, prothrombin time (PT) or activated partial thromboplastin time (aPTT) must be ≤1.5 × ULN. If a participant is receiving anticoagulant therapy, PT or aPTT must be within therapeutic range of intended use of anticoagulants. 10. Female patients of childbearing potential must have a negative serum pregnancy test at screening and a negative (serum or urine) pregnancy test within 72 hours before the first dose of study drug. If the urine test is positive or cannot be confirmed negative, a serum pregnancy test will be required and must be negative for the patient to be eligible. 11. Female patients must not be breastfeeding. 12. Female patients of childbearing potential must be willing to use a highly effective contraception method prior to study entry, while on study drug, and for a period of at least 4 months following the last dose of study drug. Note: Women receiving estrogen-based contraceptives will be excluded from the study. Note: A woman is considered of childbearing potential unless she is postmenopausal (\>1 year without menses and confirmed with a follicle-stimulating hormone test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure. Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (eg, male condom with diaphragm or male condom with cervical cap) upon study entry, while on study drug, and for a period of at least 4 months following the last dose of study drug. Males must agree to refrain from donating sperm during this period. 13. Highly effective contraception is defined as a method of contraception that has a \<1% failure rate when used consistently and correctly (as defined by the International Council for Harmonization Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Research M3 \[R2\]). These methods include implants, injectables, combined hormonal contraceptives (eg, combined oral contraceptives \[excluding estrogen-based contraceptives\], patch, and vaginal ring), some intrauterine devices (IUDs) (eg, IUD or intrauterine system), sexual abstinence, or a monogamous relationship with a vasectomized partner. a. True abstinence, when in line with the preferred and usual lifestyle of the patient, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug (ie, 60 days after discontinuing study drug or 5 times the terminal elimination half-life, whichever is longer). Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 14. Be able to understand and voluntarily sign a written informed consent form and is willing and able to comply with protocol requirements.