Salman Punekar, MD
About
Research
Publications
2024
AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors.
Mitchell S, Khan B, Payumo F, Chiorean E, Gahvari Z, Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Punekar S, Schoenfeld A, Zhao D, Vallaster M, Nagorsen D. AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps8650-tps8650. DOI: 10.1200/jco.2024.42.16_suppl.tps8650.Peer-Reviewed Original ResearchOptimal biological doseCD8+ T cellsAutologous CD4+Advanced/metastatic solid tumorsT cellsSolid tumorsSwitch receptorsDose expansionDose escalationCD4+Transgenic TCRMechanism of actionDose-limiting toxicity observation periodRecommended phase 2 doseT cell cytotoxic activityIncreased T cell activationCD4+ T cellsHelper T cell responsesPreventing T cell exhaustionPost-treatment follow-up periodChimeric switch receptorsPhase 2 doseImmunosuppressive tumor microenvironmentT cell exhaustionDuration of responseEVEREST-1: A seamless phase 1/2 study of A2B530, a carcinoembryonic antigen (CEA) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH).
Molina J, Simeone D, Smith C, Welling T, Kirtane K, Grierson P, Morelli M, Hecht J, Patel S, Locke F, Weng W, Fakih M, Vong J, Liechty K, Ng E, Welch J, Maus M, Maloney D, Go W, Punekar S. EVEREST-1: A seamless phase 1/2 study of A2B530, a carcinoembryonic antigen (CEA) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). Journal Of Clinical Oncology 2024, 42: tps2698-tps2698. DOI: 10.1200/jco.2024.42.16_suppl.tps2698.Peer-Reviewed Original ResearchOff-tumor toxicityT-cell therapyCAR-T cell therapyChimeric antigen receptorHLA-A*02T cellsCarcinoembryonic antigenHLA LOHNormal cellsCEA expressionSolid tumorsRecommended phase 2 doseLack of tumor-specific targetsNon-small cell lungDose-escalation portionPhase 2 doseDose-expansion phaseT-cell engagersObjective of Phase 1Tumor-specific targetingTreating solid tumorsT cell receptorOn-targetBayesian optimal interval designCheckpoint inhibitorsAn open-label, phase 1, multicenter study to evaluate the safety and preliminary anti-tumor activity of NT-112 in human leukocyte antigen-C*08:02–positive adult patients with unresectable, advanced, and/or metastatic solid tumors that are positive for the KRAS G12D mutation.
Punekar S, Pelster M, Becerra C, Hecht J, Paulson A, Grierson P, Morelli M, Leidner R, Kamgar M, Baranda J, Kazmi S, Shergill A, Robinson A, Patel A, Yan Y, van Heijst J, Demars N, Perez A, Cohen S, Fakih M. An open-label, phase 1, multicenter study to evaluate the safety and preliminary anti-tumor activity of NT-112 in human leukocyte antigen-C*08:02–positive adult patients with unresectable, advanced, and/or metastatic solid tumors that are positive for the KRAS G12D mutation. Journal Of Clinical Oncology 2024, 42: tps2677-tps2677. DOI: 10.1200/jco.2024.42.16_suppl.tps2677.Peer-Reviewed Original ResearchT cell receptor-engineered T cellsPancreatic ductal adenocarcinomaKRAS G12D mutationG12D mutationT cellsHLA-C*08:02Open-labelSolid tumorsDriver mutationsTCR-T cell therapyLandscape of cancer treatmentPreliminary anti-tumor activityPotential anti-tumor activityRECIST v1.1 criteriaDose-limiting toxicityTargetable driver mutationsDose-escalation studyCD8 T cellsMetastatic solid tumorsOncogenic driver mutationsAscending dose levelsSolid tumor malignanciesLimited treatment optionsFDA-approved therapiesRecombinant IL-2EVEREST-2: A seamless phase 1/2 study of A2B694, a mesothelin (MSLN) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors that show MSLN expression and human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH).
Punekar S, Hecht J, Smith C, Simeone D, Dorigo O, Boyd L, Kirtane K, Ward J, Locke F, Morelli M, Block M, Eskander R, Langeberg W, Liechty K, Ong G, Go W, Maloney D, Maus M, Welch J, Molina J. EVEREST-2: A seamless phase 1/2 study of A2B694, a mesothelin (MSLN) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors that show MSLN expression and human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). Journal Of Clinical Oncology 2024, 42: tps2699-tps2699. DOI: 10.1200/jco.2024.42.16_suppl.tps2699.Peer-Reviewed Original ResearchChimeric antigen receptorOff-tumor toxicityT-cell therapyCAR-T cell therapyMesothelin expressionT cellsHLA-A*02Solid tumorsNormal cellsChimeric antigen receptor T cellsRecommended phase 2 doseCAR T cell activityLack of tumor-specific targetsNon-small cell lung cancerCryopreserved T cellsMajor body cavitiesPhase 2 doseDose-expansion phaseObjective of Phase 1Tumor-specific targetingCell lung cancerSolid tumor typesFirst-in-humanT cell activationOn-targetA phase IV study of ApricityCARE program for cancer adverse events rapid evaluation to improve treatment outcomes of ethnic/racial minority patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI).
Henick B, Veluswamy R, Halmos B, Labbe K, Sender N, Sta Ana S, Chen L, Punekar S, Singh J, Lee M, Shu C, Herzberg B, Chin L, Velcheti V. A phase IV study of ApricityCARE program for cancer adverse events rapid evaluation to improve treatment outcomes of ethnic/racial minority patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI). Journal Of Clinical Oncology 2024, 42: tps1642-tps1642. DOI: 10.1200/jco.2024.42.16_suppl.tps1642.Peer-Reviewed Original ResearchNon-small cell lung cancerIncidence of immune-related adverse effectsImmune checkpoint inhibitorsRun-in phaseTreatment landscape of non-small cell lung cancerNon-small cell lung cancer patientsImmune checkpoint inhibitor useImmune-related adverse effectsDiagnosis of non-small cell lung cancerICI-treated patientsEarly treatment discontinuationMinority patientsCell lung cancerEarly-stage diseasePhase IV studyImprove treatment outcomesStandard of carePotential poor outcomesHealth literacy levelsReduce health disparitiesCheckpoint inhibitorsEthnic minority patientsEthnic/racial minority patientsTreatment discontinuationHealth care resourcesOverall survival (OS) in a u.s. Asian population with stage IV NSCLC with EGFR mutations treated with first-line (1L) osimertinib (Osi) compared to earlier generation (Gen) of TKIs or sequential treatment (Tx).
Liu Y, Ma Z, Moreira A, Chachoua A, Velcheti V, Lau S, Punekar S, Sabari J, Shum E. Overall survival (OS) in a u.s. Asian population with stage IV NSCLC with EGFR mutations treated with first-line (1L) osimertinib (Osi) compared to earlier generation (Gen) of TKIs or sequential treatment (Tx). Journal Of Clinical Oncology 2024, 42: e20597-e20597. DOI: 10.1200/jco.2024.42.16_suppl.e20597.Peer-Reviewed Original ResearchNon-small-cell lung cancerTyrosine kinase inhibitorsStage IV non-small-cell lung cancerIV non-small-cell lung cancerOverall survivalCox proportional-hazards modelRetrospective studyProportional-hazards modelMedian OSMetastatic non-small-cell lung cancerHazard ratioIRB-approved retrospective studyMultivariate Cox proportional-hazards modelProgression-free survivalYears of follow-upKaplan-Meier methodLog-rank testAssess survival differencesCalculate hazard ratiosFLAURA trialL858R patientsNSCLC ptsSequential afatinibSuperior OSEGFR mutationsConsolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study
Nassar A, Kim S, Aredo J, Feng J, Shepherd F, Xu C, Kaldas D, Gray J, Dilling T, Neal J, Wakelee H, Liu Y, Lin S, Abuali T, Amini A, Nie Y, Patil T, Lobachov A, Bar J, Fitzgerald B, Fujiwara Y, Marron T, Thummalapalli R, Yu H, Owen D, Sharp J, Farid S, Rocha P, Arriola E, D'Aiello A, Cheng H, Whitaker R, Parikh K, Ashara Y, Chen L, Sankar K, Harris J, Nagasaka M, Ayanambakkam A, Velazquez A, Ragavan M, Lin J, Piotrowska Z, Wilgucki M, Reuss J, Luders H, Grohe C, Baena Espinar J, Feiner E, Punekar S, Gupta S, Leal T, Kwiatkowski D, Mak R, Adib E, Naqash A, Goldberg S. Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study. Journal Of Thoracic Oncology 2024, 19: 928-940. PMID: 38278303, DOI: 10.1016/j.jtho.2024.01.012.Peer-Reviewed Original ResearchTreatment-related adverse eventsConcurrent chemoradiationConsolidation therapyConsolidation durvalumabOverall survivalEGFR-mutant non-small-cell lung cancerAny-grade TRAEsCommon Terminology Criteria for Adverse Events versionFollow-upReal-world progression-free survivalObservational cohortNon-small-cell lung cancerPatients treated with osimertinibEGFR tyrosine kinase inhibitorsMedian duration of treatmentMulticenter retrospective cohort studyMultivariate Cox regression analysisDefinitive concurrent chemoradiationInternational retrospective analysisOptimal consolidation therapySensitive EGFR mutationsTreated with durvalumabAdverse Events versionProgression-free survivalStage III NSCLC
2023
Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma
Dolgalev I, Zhou H, Murrell N, Le H, Sakellaropoulos T, Coudray N, Zhu K, Vasudevaraja V, Yeaton A, Goparaju C, Li Y, Sulaiman I, Tsay J, Meyn P, Mohamed H, Sydney I, Shiomi T, Ramaswami S, Narula N, Kulicke R, Davis F, Stransky N, Smolen G, Cheng W, Cai J, Punekar S, Velcheti V, Sterman D, Poirier J, Neel B, Wong K, Chiriboga L, Heguy A, Papagiannakopoulos T, Nadorp B, Snuderl M, Segal L, Moreira A, Pass H, Tsirigos A. Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma. Nature Communications 2023, 14: 6764. PMID: 37938580, PMCID: PMC10632519, DOI: 10.1038/s41467-023-42327-x.Peer-Reviewed Original ResearchConceptsTumor-adjacent tissuesDisease progressionInflammatory signatureEarly-stage lung adenocarcinoma patientsSuccessful surgical resectionLong-term patientsInflammatory gene signatureLung adenocarcinoma patientsStrongest clinical predictorsNon-immune cellsNormal lung tissuesAdjacent normal tissuesCancer Genome AtlasSurgical resectionClinical predictorsClinical outcomesAdenocarcinoma patientsPredictive biomarkersWorse outcomesLung tissueDisease outcomeLung adenocarcinomaHigh riskSingle-cell transcriptomic analysisGene signature634 EVEREST-1: A seamless phase 1/2 study of CEA logic-gated Tmod CAR T-cell therapy (A2B530) in patients with solid tumors associated with CEA expression also exhibiting HLA loss of heterozygosity (LOH)
Punekar S, Welling T, Randolph Hecht J, Molina J, Smith C, Garon E, Pia Morelli M, Fakih M, Kirtane K, Grierson P, Patel S, Lin Y, Kopetz S, Locke F, Ward J, Lozac’hmeur A, Frigault M, Nikiforow S, Weng W, Specht J, Dragovich T, Vong J, Mardiros A, Liechty K, Go W, Welch J, Ng E, Maus M, Maloney D, Simeone D. 634 EVEREST-1: A seamless phase 1/2 study of CEA logic-gated Tmod CAR T-cell therapy (A2B530) in patients with solid tumors associated with CEA expression also exhibiting HLA loss of heterozygosity (LOH). 2023, a724-a725. DOI: 10.1136/jitc-2023-sitc2023.0634.Peer-Reviewed Original ResearchEP12.01-38 Real-world Outcomes in a U.S. Asian Population with Stage IV NSCLC Treated with Osimertinib Stratified by EGFR Subtype
Liu Y, Bi J, Moreira A, Chachoua A, Velcheti V, Lau S, Punekar S, Sabari J, Shum E. EP12.01-38 Real-world Outcomes in a U.S. Asian Population with Stage IV NSCLC Treated with Osimertinib Stratified by EGFR Subtype. Journal Of Thoracic Oncology 2023, 18: s655-s656. DOI: 10.1016/j.jtho.2023.09.1254.Peer-Reviewed Original Research