Inclusion Criteria:

Male or non-pregnant, non-lactating female participants age ≥18 years.

Histologically or cytologically confirmed solid tumors (see details below):

For the dose escalation, the following solid tumors are allowed in participants who have developed disease progression through standard therapy and in participants for whom standard of care therapy that prolongs survival is unavailable or unsuitable (according to the Investigator), which include non-small cell lung cancer (NSCLC), locally advanced/metastatic breast cancer, hormone receptor positive breast cancer and human epidermal growth factor receptor 2 negative breast cancer, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma (PDAC), soft tissue sarcoma (STS), hepatocellular carcinoma (HCC), and kidney cancer.

1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
2. Participant must have at least 1 measurable lesion Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (by local Investigator) except participants with bone-only metastatic breast cancer (mBC) who can be enrolled without measurable disease. Participant must have radiographic evidence of disease progression based on RECIST criteria following the most recent line of treatment.
3. Life expectancy of >3 months, in the opinion of the Investigator.
4. Clinical sites must provide participants' archived tissue or conduct fresh tumor biopsy. Fresh biopsy pre-treatment is preferred, archival tissue (the most recent available) is acceptable if fresh biopsy is not performed at Screening. Both fresh and archival tissue samples must be collected by core needle biopsy or surgical resection. Fine needle aspirates are not permitted.

Exclusion Criteria:

1. History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for >2 years or cancer of low risk of recurrence if agreed to by the medical monitor, except any treated or monitored indolent cancer that is unlikely to cause mortality in 5 years.
2. Known symptomatic brain metastases requiring >10 mg/day of prednisolone (or its equivalent) at the time of signing informed consent. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of PYX-201 treatment, fulfill the steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥4 weeks after treatment.
3. Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment at the start of PYX-201 treatment.
4. Major surgery within 4 weeks prior to the start of PYX-201 treatment, as defined by the Investigator.
5. Prior solid organ or bone marrow progenitor cell transplantation.