∙ Eligible participants must meet the following inclusion criteria. The criteria below apply to participants enrolling in Phase 1 and Phase 2, unless otherwise specified.

• Have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation.

• Be ≥ 18 years of age at the time the ICF is signed.

• Have consented to submission of fresh or archival tumor tissue, if available.

• Have adequate organ function confirmed by the following laboratory values obtained within the Screening Period prior to administration of \[68Ga\]Ga FAP 2286 and prior to first cycle of chemotherapy in the combination groups:

• a. Bone Marrow Function (independent of transfusion or growth factor support within 21 days prior to planned first administration of \[177Lu\]Lu FAP 2286): i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; ii. Platelets \> 100 × 109/L; and iii.Hemoglobin ≥ 9 g/dL. b. Hepatic Function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × institutional upper limit of normal (ULN); if liver metastases, then ≤ 5 × the institutional ULN; ii. Serum Bilirubin ≤ 1.5 × institutional ULN or if known Gilbert's syndrome then ≤ 3 × institutional ULN; iii. Serum albumin ≥ 30 g/L (3 g/dL) and iv. INR ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT)≤1.5 x ULN. This applies to participants who are not receiving therapeutic anticoagulation, participants receiving therapeutic anticoagulation should be on a stable dose.

• c. Renal Function: i. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min using the Cockcroft Gault formula.

• Have an Eastern Oncology Group (ECOG) performance status of 0 or 1.

• Have a life expectancy of ≥ 6 months.

• Have measurable disease per RECIST v1.1 meeting the following criteria:

‣ At least 1 lesion of ≥ 10 mm in the longest diameter for a non lymph node or ≥ 15 mm in the short axis diameter for a lymph node that is serially measurable according to RECIST v1.1 using conventional CT and/or MRI.

‣ • Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation must show subsequent evidence of substantial size increase to be deemed a target lesion.

‣ For Phase 1 only:

• Have a histologically and/or cytologically confirmed advanced/metastatic solid tumor not amenable to treatment with curative intent:

• a. Tumor must be refractory to or have progressed following prior treatment and have no satisfactory alternative treatment options.

• For Phase 2 only:

• Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below:

• a. Pancreatic Cancer monotherapy group: i. Pancreatic ductal adenocarcinoma (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded) ii. Participants must have progressed after at least 1, but no more than two prior chemotherapy regimens for locally advanced unresectable or metastatic disease.

• Criteria b through h removed during Protocol amendment 7. i. Pancreatic Cancer combination group (with mFOLFIRINOX) i. Pancreatic ductal adenocarcinoma (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded); ii. Participants have not received prior systemic therapy for metastatic disease.

• j. Non-small cell lung cancer monotherapy group i. Non-small cell lung cancer (adenocarcinoma and squamous eligible; endocrine, neuroendocrine and small cell tumors are excluded) ii. Participants must have progressed after at least 1 but not more than 2 prior systemic regimens including chemotherapy and immunotherapy. Participants with NSCLC and targeted therapy treatment options, are eligible for the clinical trial as long as they meet these criteria (progression after 1 or 2 prior therapies). Note: Participants with NSCLC harboring mutations amenable to targeted therapy treatment, are eligible if received targeted therapy as single agent or in combination in 1st or 2nd line of treatment; participants not eligible to receive such therapies in 1st or 2nd line are also eligible to participate to the study.

• iii. Participants who have received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and an immune checkpoint inhibitor and developed recurrent or metastatic disease while on or within 12 months of completing therapy are eligible. Participants with NSCLC and targeted therapy treatment options are eligible for the clinical trial as long as they meet these criteria.

• iv. Participants with recurrent disease \> 12 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen and an immune checkpoint inhibitor (given either together or sequentially to treat the recurrence), are eligible v. Participants must have received platinum-based chemotherapy for advanced or metastatic disease and immune checkpoint inhibitor either together (in the same line of treatment) or sequentially (two different lines of treatment) and then progressed.

• k. Non small cell lung cancer combination group i. Non-small cell lung cancer (adenocarcinoma and squamous eligible; endocrine, neuroendocrine and small cell tumors are excluded) ii. Participants must have progressed after at least 1 but not more than 2 prior systemic regimens including chemotherapy and immunotherapy. Participants with NSCLC and targeted therapy treatment options, are eligible for the clinical trial as long as they meet these criteria (progression after 1 or 2 prior therapies). Note: Participants with NSCLC harboring mutations amenable to targeted therapy treatment, are eligible if received targeted therapy as single agent or in combination in 1st or 2nd line of treatment; participants not eligible to receive such therapies in 1st or 2nd line are also eligible to participate to the study.

• iii. Participants who have received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and an immune checkpoint inhibitor and developed recurrent or metastatic disease while on or within 12 months of completing therapy are eligible iv. Participants with recurrent disease \> 12 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen and an immune checkpoint inhibitor (given either together or sequentially to treat the recurrence), are eligible v. Participants must not have received prior taxane therapy either as monotherapy or in combination.

• l. Breast cancer monotherapy group i. HR positive HER2 negative

• • Participant has a histologically and/or cytologically documented diagnosis of HR positive HER2 negative metastatic breast cancer (based on the most recently analyzed tissue sample tested by a local laboratory).

⁃ Participants must have progressed on at least one line of hormone-based therapy (either alone or in combination) and at least one, but not more than two lines of chemotherapy (including cytotoxic, targeted and/or anti-drug conjugate therapies) for metastatic disease.

• ii. HER2 positive

• • Participant has a histologically and/or cytologically documented diagnosis of HER2 positive metastatic breast cancer (based on the most recently analyzed tissue sample tested by a local laboratory).

• • Participant must have progressed on at least two lines of HER2 targeted therapy for metastatic disease.

• iii. Triple negative breast cancer (TNBC)

• • Participant has a histologically and/or cytologically documented diagnosis of TNBC (based on the most recently analyzed tissue sample tested by a local laboratory).

⁃ Participants must have progressed on at least two lines of cytotoxic chemotherapy (including cytotoxic, anti-drug conjugate, targeted therapies and/or IO) for metastatic disease.