This is a study to investigate the safety and efficacy of an investigational OBX-115 regimen in adult participants with advanced solid tumors.

Primary Objective (Phase 1):

• Assess the safety and tolerability of OBX-115 regimen

Primary Objective (Phase 2):

• Evaluate preliminary efficacy of OBX-115 regimen as measured by Blinded Independent Central Review (BICR) using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Cohort 3)
• Evaluate preliminary efficacy of OBX-115 regimen as measured by the investigator using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Cohorts 1, 2, 4)

Secondary (Phase 1):

• Assess preliminary efficacy of OBX-115 regimen by evaluating ORR

Secondary (Phase 2):

• Evaluate safety and tolerability of OBX 115 based on the collected AE data

Secondary (both Phase 1 and Phase 2):

• Evaluate duration of response (DOR): To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by BICR until disease progression or death due to cancer (Phase 2 Cohort 3).
• Evaluate duration of response (DOR): To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator until disease progression or death due to cancer (Phase 1 and Phase 2 Cohorts 1, 2, and 4).
• Evaluate disease control rate (DCR): To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) for at least 4 weeks per RECIST v1.1 as assessed by BICR (Phase 2 Cohort 3).
• Evaluate disease control rate (DCR): To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) for at least 4 weeks per RECIST v1.1 as assessed by the investigator (Phase 1 and Phase 2 Cohorts 1, 2, and 4).
• Evaluate progression-free survival (PFS): To evaluate the time from the date of OBX-115 infusion until disease progression per RECIST v1.1 as assessed by BICR or death due to any cause (Phase 2 Cohort 3).
• Evaluate progression-free survival (PFS): To evaluate the time from the date of OBX-115 infusion until disease progression per RECIST v1.1 as assessed by the investigator or death due to any cause (Phase 1 and Phase 2 Cohorts 1, 2, and 4).
• Evaluate overall survival (OS): To evaluate the time from the date of OBX-115 infusion to death due to any cause
• Evaluate feasibility of the manufacturing process: Evaluated as the proportion of OBX-115 products initiated for manufacturing that pass release criteria for infusion.

Inclusion Criteria:

1. Participant must be 18 years of age or older at the time of signing the informed consent.

2. Participant has a histologically confirmed diagnosis of advanced/metastatic melanoma or relapsed refractory metastatic non-small cell lung cancer (NSCLC).

3. Cohort and indication specific criteria as follows:

   1. Phase 1 and Phase 2 Cohort 1 (enrollment complete):

      • Participants with unresectable or metastatic melanoma must have experienced documented radiographic disease progression after systemic therapy containing a programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking antibody.
      • Participants with melanoma must not exceed 2 prior lines of systemic therapy. Neoadjuvant/Adjuvant treatment will not be considered a prior line of systemic therapy unless the participant progressed during or within the 12 weeks after the last dose of the adjuvant PD-1/PD-L1 blocking antibody.

   2. Phase 1 and Phase 2 Cohort 2 (recruiting):

      • Participants with non-small cell lung cancer should have relapsed or are refractory to approved systemic therapies (approved ICI-based regimen for all appropriate participants and/or an approved targeted therapy for known molecular abnormalities if applicable to their disease).
      • Participant must not have been exposed to any second line cytotoxic chemotherapy if they have already received cytotoxic chemotherapy in the first line setting.

   3. Phase 2 Cohort 3 (recruiting):

      • Participants with unresectable or metastatic melanoma must have experienced documented radiographic disease progression after systemic therapy containing a programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking antibody.
      • Participants with melanoma must not exceed 2 prior lines of systemic therapy. Neoadjuvant/Adjuvant treatment will not be considered a prior line of systemic therapy unless the participant progressed during or within the 12 weeks after the last dose of the adjuvant PD-1/PD-L1 blocking antibody.
      • Participants with targetable BRAF mutations are not required to have received prior BRAF inhibitors. Participants must not have disease progression on a BRAF/MEK inhibitor that was given as the most recent line of therapy.

   4. Phase 2 Cohort 4 (recruiting):

      • Participants with frontline unresectable or metastatic melanoma.
      • Participants may have received up to 2 doses of system therapy containing a programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking antibody-based treatment of unresectable metastatic melanoma (but must not have known clinical progression.) Neoadjuvant/Adjuvant treatment will not be considered a prior line of systemic therapy; however, participants whose disease progressed within 12 weeks after the last dose of the PD-1/PD-L1 blocking antibody given as adjuvant treatment (primary ICI resistant) are not eligible.

4. Participant is assessed as having at least one lesion (or aggregate lesions) suitable for OBX-115 generation.

5. After tumor tissue procurement, the participant will have at least one remaining measurable lesion, as defined by RECIST v1.1.

6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of greater than 6 months.

7. Participant has recovered from all prior anticancer treatment-related AEs to at least Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE]).

8. Participants must have completed post-operative recovery from any prior surgical procedures with wound healing and resolution of all surgical complications prior to planned tumor procurement surgery.

9. Both male and female (women of childbearing potential) participants agree to the follow protocol specified contraceptive and/or abstinence requirements.

10. Participant has protocol specified hematologic parameters for absolute neutrophil count (ANC) and platelet count.

11. Participant has adequate cardiac, liver, lung, and kidney organ function as specified in the protocol.

Exclusion Criteria:

1. Participant has melanoma of uveal origin or its other genetic equivalents (e.g. GNA11 and GNAQ).
2. Participant has a history of brain metastases or leptomeningeal disease. Participants may be considered for enrollment if they have 4 or fewer brain metastatic lesions that are that have been treated, if clinically indicated. Asymptomatic brain metastases that are equivocal or too small to warrant treatment may not be counted towards the above set limits upon discussion and agreement from the Medical Monitor.
3. Participant has an active medical illness(es) that, in the opinion of the Investigator, would pose increased risks for study participation.
4. Participants with non-small cell lung cancer with refractory and clinically significant pleural effusions.
5. Participant has any form of primary or acquired immunodeficiency.
6. Participant has a history of hypersensitivity to any component of the study intervention.
7. Participant had another primary malignancy within the previous 3 years (with protocol specified exceptions).
8. Participant has a history of allogeneic organ transplant, allogeneic cell therapy, or genetically engineered cell therapy. Prior engineered TIL cell therapy is allowed.
9. Participant requires systemic steroid therapy of greater than10 mg/day of prednisone or equivalent.
10. Participant received a live or attenuated vaccination within 28 days prior to the start of lymphodepletion (LD).
11. Participant has evidence of positive infectious disease screening and/or any active uncontrolled viral, bacterial, or fungal disease requiring ongoing systemic treatment or identified during screening.