Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma

Inclusion Criteria:

* Age \>=18 years of age or older on the date of signing informed consent.
* Histologically confirmed diagnosis of secretory multiple myeloma with myeloma markers at levels defined in the protocol.
* Documented diagnosis of relapsed and refractory multiple myeloma (RRMM) (at least 3 prior regimens and responsive to at least 1, and refractory to most recent prior therapies, which must have included one or more than one drug from each of the following drug classes: an immunomodulatory imide drug (IMiD), proteasome inhibitor, alkylator (unless the participant is ineligible or contraindicated to receive an alkylator), CD 38 monoclonal antibody, and glucocorticoid as separate lines or a combined line of therapy.- Left ventricular ejection fraction (LVEF) \>= 50%. Lower LVEF (\>= 40%) permissible if formal cardiologic evaluation reveals no evidence for clinically significant functional impairment.
* Meets protocol criteria for patients who have previously received checkpoint inhibitors or other immuno-oncology agents.
* ECOG Performance Status 0 or 1.
* Participant is HLA-A\*02:01, HLA-A\*02:05, and/or HLA-A\*02:06 positive as determined by a designated central laboratory.
* Participant has confirmed sufficient expression of NY-ESO-1 and/or LAGE-1a as determined by a designated central laboratory.
* In the Investigator's opinion, the participant is fit for cell collection.
* Participant has adequate organ function and cell counts as described in the protocol.
* Participants previously treated with BCMA therapy (BCMA chimeric antigen receptor (CAR)-T, antibody-drug conjugate (ADC), or other type of BCMA-targeted therapy) must have progressed from this therapy prior to attending the Baseline visit prior to beginning lymphodepletion.
* Contraception use by male and female participant meets protocol requirements.

Exclusion Criteria:

* Has only plasmacytomas, plasma cell leukemia, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), non-secretory myeloma or primarily amyloidosis.
* Previously received anti- programmed death (PD)-1, anti-PD-ligand (L)1, or anti-PD-L2 inhibitor.
* Previously participated in Merck pivotal trial NCT02576977: Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab in Refractory or RRMM.
* Had a prior allogeneic stem cell transplant.
* Has ongoing toxicity from previous anticancer therapy.
* Had a major surgery within 4 weeks prior to enrollment.
* Has history of allergic reactions to fludarabine, cyclophosphamide or agents similar to fludarabine, cyclophosphamide or other agents used in the study.
* Known history of myelodysplasia.
* Current active liver or biliary disease.
* Known history of chronic active hepatitis or liver cirrhosis.
* Participant has an active viral infection.
* History of severe immune disease, including non-infectious pneumonitis, requiring steroids or other immunosuppressive treatments.
* Active immune-mediated diseases.
* Prior or active demyelinating disease.
* Evidence or history of significant cardiac disease.
* Evidence or history of other significant, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease.
* Participants with concomitant second malignancies (except adequately treated non-melanomatous skin cancers, carcinoma in situ of the breast, treated superficial bladder cancer or prostate cancer, or in situ cervical cancers ) not in complete remission.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may be eligible.
* Active bacterial or systemic viral or fungal infections.
* Pregnant or breastfeeding.
* Cannot meet washout periods for prior radiotherapy, chemotherapy or other protocol-specified therapies.
* More than 2 years have passed since the participant's last leukapheresis collection.