Clinical Trial Finder

Inclusion Criteria:

• - Histologic or cytologic confirmation of advanced solid tumor.

• - For LY3300054 + abemaciclib only: No participants with liver metastases.

Participants must have normal aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin.

• - For LY3300054 + abemaciclib in HR+, HER- breast cancer: - Express at least 1 of the hormone receptors [HR; estrogen receptor (ER) or progesterone receptor (PR)] by immunohistochemistry (IHC) to fulfill the requirement for HR+ disease on the primary tumor or metastatic lesion of the breast cancer.

ER and PR assays are considered positive if there is at least 1% positive tumor nuclei in their sample as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) or local guidelines.

• - To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP or local guidelines.

• - Most recent HR and HER2 receptor testing should be used to determine eligibility.

• - Have previously received prior treatment with at least 1 but no more than 3 chemotherapy regimens in the metastatic setting.

• - Have AST, ALT, GGT, and AP that are ≤2.5x upper limit of normal (ULN) and normal bilirubin (total and direct) regardless of liver involvement.

• - For LY3300054 + merestinib in pancreatic cancer: - Histologically or cytological confirmed diagnosis of metastatic or locally advanced, unresectable pancreatic adenocarcinoma (excluding other pancreatic malignancies for example, acinar cell carcinomas, adenosquamous carcinomas, and neuroendocrine islet cell neoplasms).

• - Have had disease progression, be refractory or intolerant to no more than 2 prior systemic regimens.

• - For LY3300054 + LY3321367 in PD-1/PD-L1-naive, MSI-H/MMR-deficient advanced solid tumors: - Have histologically or cytologically confirmed diagnosis of advanced solid tumor AND shown to be MSI-H or MMR-deficient.

• - For LY3300054 + LY3321367 in PD-1/PD-L1- resistant/refractory, MSI-H/MMR-deficient advanced solid tumors: - Have histologically or cytologically confirmed diagnosis of advanced solid tumor AND shown to be MSI-H or MMR-deficient.

• - Prior exposure to PD-1/PD-L1 agent regardless of response.

• - For Phase 1b LY3300054 monotherapy or combination therapy, no prior treatment with a PD-1 or PD-L1 agent is allowed.

• - Exception: the LY3321367 combination in participants with PD-1/PD-L1- resistant/refractory, MSI-H, where prior exposure to PD-1/PD-L1 agent required.

• - For Phase 1a LY3300054 monotherapy or combination therapy, previous immunotherapy is acceptable if the following criteria are met: - Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.

• - Must have completely recovered or recovered to baseline prior to screening from any prior adverse events (AEs) occurring while receiving prior immunotherapy.

• - Must not have experienced a Grade ≥3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy.

• - Must not have required the use of additional immunosuppressive agents other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of >10 milligrams prednisone or equivalent per day.

• - Have at least 1 measurable lesion assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• - Have adequate organ function.

• - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

• - Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator.

• - Have submitted a tumor tissue sample, as follows: - For participants entering the Phase 1a dose escalation: have submitted, if available, the most recent archival tumor tissue sample.

• - For those participating ONLY in Phase 1b expansions: Have submitted tumor tissue sample from a newly obtained core or excisional biopsy for a tumor lesion (preferred) or a recent biopsy taken with 3 months prior to study enrollment and following the participants most recent prior systemic treatment and be willing to undergo a biopsy procedure during the study treatment period for collection of additional tumor tissue sample.

Exclusion Criteria:

• - Have a serious concomitant systemic disorder including human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorder or disease requiring high dose of steroids.

• - Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea.

• - Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.

• - Have an active infection requiring systemic therapy.

• - Have moderate or severe cardiovascular disease.

• - Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment.

• - Have received a live vaccine within 30 days before the first dose of study treatment.

• - Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment.

Arms

Experimental: LY3300054

LY3300054 given intravenously (IV) on day 1 and day 15 of a 28 day cycle or LY3300054 given IV on day 1 of a 21 (or 28) day cycle.

Experimental: LY3300054 + Ramucirumab

LY3300054 and ramucirumab given IV on day 1 and day 15 of a 28 day cycle or ramucirumab given IV on day 1 and day 8 and LY3300054 given IV on day 1 of a 21 day cycle.

Experimental: Abemaciclib + LY3300054

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.

Experimental: LY3300054 + Abemaciclib (Concurrent Dosing)

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.

Experimental: LY3300054 + Abemaciclib

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle. This arm will only be initiated if required.

Experimental: LY3300054 + Merestinib

LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.

Experimental: LY3300054 Expansion (Metastatic Cutaneous Melanoma)

LY3300054 given IV on day 1 and day 15 of a 28 day cycle.

Experimental: LY3300054 Expansion (MSI-H Solid Tumors)

LY3300054 given IV on day 1 and day 15 of a 28 day cycle.

Experimental: : LY3300054 + Abemaciclib (HR+, HER2- Breast Cancer) Expansion

LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.

Experimental: LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H)

LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.

Experimental: LY3300054 + LY3321367 Expansion

LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.

Experimental: LY3300054 + Merestinib (Pancreatic Cancer) Expansion

LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.

Interventions

Drug: - LY3300054

Administered IV

Drug: - Ramucirumab

Administered IV

Drug: - Abemaciclib

Administered orally

Drug: - Merestinib

Administered orally

Drug: - LY3321367

Administered IV