⁃ Phase 1:

• Males and females ≥18 years of age at the time of consent

• Willingness and capacity to provide written consent

• Patients who have histologically or cytologically-documented, unresectable locally advanced, or metastatic solid malignancy or designated lymphoma that is progressing or has failed the therapies listed below or who are intolerant of or are ineligible for or refuse standard of care therapy as detailed below.

‣ Patients previously pre-treated with a checkpoint inhibitor must be anti-PD-L1 relapsed/refractory defined as having clear evidence of radiologic or clinical progression while on or within 4 months of their last anti-PD-L1 dose.

⁃ There is no limit to the number of prior treatment regimens a patient may have had prior to enrollment.

• Has one of the following solid tumor or lymphoma indications:

⁃ Non-small cell lung cancer (NSCLC) - squamous or non-squamous:

• Must have received prior chemotherapy and a checkpoint inhibitor (either sequentially or in combination) per PD-L1 status

∙ Must not have a documented EGFR, ALK, ROS, RET, BRAFV600E, Met exon 14 skipping, KRAS mutation

⁃ Head and neck squamous cell carcinoma (HNSCC) HPV+ or -:

• Must have received prior treatment with a platinum-based chemotherapy and a checkpoint inhibitor (either sequentially or in combination) per PD-L1 status

⁃ Triple negative breast cancer (TNBC):

• Must have received prior treatment with chemotherapy (anthracycline, and/or taxanes, and/or platinum, and/or gemcitabine); sacituzumab govitecan; a checkpoint inhibitor if PD-L1+; a PARPi for patients with gBRCA mutations

⁃ Cutaneous squamous cell carcinoma:

• Must have received prior treatment with a checkpoint inhibitor

⁃ Hormone receptor positive (HR+) breast cancer:

‣ \- Must have received endocrine therapy, a CDK 4/6 inhibitor (preferably in combination with endocrine therapy in the 1st line or 2nd line setting or as monotherapy), a PI3K inhibitor and endocrine therapy for tumors with PIK3CA activating mutation; and a PARPi for patients with gBRCA mutations

⁃ Small bowel carcinoma:

• Must have received prior treatment with at least one 5FU or capecitabine based regimen (such as but not limited to FOLFOX, FOLFIRI or CAPOX) with or without bevacizumab, and a PD1/PD-L1 inhibitor alone or in combination with CTLA4 inhibitor (for MSI-H or dMMR tumors)

⁃ Esophageal cancer:

• Must have received prior treatment with a platinum-based chemotherapy and a checkpoint inhibitor (either sequentially or in combination per PD-L1 status), and an anti-HER2 agent for patients with known HER2 overexpressing tumors

⁃ Colorectal cancer (MSS \& MSI-H/dMMR):

• Must have received at least one 5FU chemotherapy-based regimen, with bevacizumab or cetuximab/panitumumab, and / or a PD1/PD-L1 (single agent or combination with CTLA4) for dMMR/MSI-H tumors

∙ For patients with known BRAF V600E mutation: must have received prior treatment with a combination of encorafenib and cetuximab or panitumumab

⁃ Histologically confirmed diffuse large B cell lymphoma (DLBCL)

• Must have received at least 2 prior lines of therapy including prior treatment with chemotherapy and an anti-CD20 antibody (ie, CHOP)

∙ Must be ineligible or refuse therapies with demonstrated clinical benefit such as for example CAR-T or autologous stem cell transplant

⁃ Hodgkin lymphoma:

‣ \- Must have received at least 3 prior systemic therapies, including combination chemotherapy (ie, ABVD).

⁃ Burkitt lymphoma:

• Must have received at least 2 prior lines of therapy

∙ Must be ineligible or refuse therapies with demonstrated clinical benefit

⁃ Follicular lymphoma:

• Must have received 3 prior lines of therapy, and must have received rituximab and chemotherapy

• Patients with solid tumors have measurable disease based on RECIST 1.1. In hematological malignancies LYRIC/Lugano will be used.

• In defined cohorts must have confirmed positive expression of CD161. Patients must have an available archival biopsy sample or agree to have a fresh biopsy obtained to confirm positivity and must agree to a mandatory newly obtained on-treatment biopsy.

⁃ Phase 1B:

⁃ Must meet all of eligibility criteria in Phase 1, AND the following:

• Must have histologically or cytologically-documented, unresectable, locally-advanced or metastatic MSS CRC with documented IHC for MMR and/or DNA for MSI consistent with MSS CRC.

• Eligible for treatment with fruquintinib according to the FDA-approved USPI

• Must have received no more than 3 lines of systemic therapy for metastatic or unresectable disease, consisting of prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Neoadjuvant or adjuvant systemic therapy is not counted as a prior line, and standard of care agents need not be repeated in the metastatic setting if not clinically indicated in the opinion of the investigator

• Body weight ≥40kg

⁃ Phase 2A: