Loading…
A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors
The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and...
Saved in:
| Published in: | Frontiers in pediatrics 2023-05, Vol.11, p.1183295-1183295 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3 |
| container_end_page | 1183295 |
| container_issue | |
| container_start_page | 1183295 |
| container_title | Frontiers in pediatrics |
| container_volume | 11 |
| creator | Moreno, Lucas Teira, Pierre Croop, James M Gerber, Nicolas U André, Nicolas Aerts, Isabelle Gros Subias, Luis De Wilde, Bram Bautista, Francisco Turpin, Brian Kunduri, Srinivasa Hamidi, Ali Lawrence, Tatiana Streby, Keri A |
| description | The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors.
T-VEC was delivered by intralesional injection at 10
plaque-forming units (PFU)/ml on the first day, followed by 10
PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
Fifteen patients were enrolled into two cohorts based on age: cohort A1 (
= 13) 12 to ≤21 years old (soft-tissue sarcoma,
= 7; bone sarcoma,
= 3; neuroblastoma,
= 1; nasopharyngeal carcinoma,
= 1; and melanoma,
= 1) and cohort B1 (
= 2) 2 to |
| doi_str_mv | 10.3389/fped.2023.1183295 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_f28a1250c8b1469e8458cf378d213834</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_f28a1250c8b1469e8458cf378d213834</doaj_id><sourcerecordid>2824688282</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3</originalsourceid><addsrcrecordid>eNpVkk1v3CAQhq2qVROl-QG9VBx7iDcG_AGnKor6ESlSL-0ZjWFYE2HjAt5q_1l_Xr3ZTZRwGTQz7zMMeoviI602nAt5bWc0G1YxvqFUcCabN8U5Y7ItGW-rty_uZ8VlSg_VemRXNbR5X5zxjknGu_a8-HdD5gESEnpFrIspl24q9eC8uSLj4rPTOGWMJOXF7EkOBHfgF8hI8oAkgcW8JzAZgtY6DXpPgn0shUkHv1_1ZMA4YyI7F5dEMng3hi1OSDwcKhBx3qEmbiLrQg5yXCUzZLfOTeSvywMBs4NJoyEpeGdIXsYQ04finQWf8PIUL4rf377-uv1R3v_8fnd7c1_qum1zyYBJzU2LTS-l6U1v6wZbsFxTyoSQTHcSG8kqYVpZy1YYbmttrWyQdUL3_KK4O3JNgAc1RzdC3KsATj0mQtwqiOuaHpVlAihrKi16WrcSRd0IbXknDKNc8HplfTmy5qUf0Ry-NoJ_BX1dmdygtmGnaMXquuPNSvh8IsTwZ8GU1eiSRu9hwrAkxQSrWyHWsLbSY6uOIaWI9nkOrdTBQergIHVwkDo5aNV8evnAZ8WTX_h_vGXG3A</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2824688282</pqid></control><display><type>article</type><title>A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors</title><source>Open Access: PubMed Central</source><creator>Moreno, Lucas ; Teira, Pierre ; Croop, James M ; Gerber, Nicolas U ; André, Nicolas ; Aerts, Isabelle ; Gros Subias, Luis ; De Wilde, Bram ; Bautista, Francisco ; Turpin, Brian ; Kunduri, Srinivasa ; Hamidi, Ali ; Lawrence, Tatiana ; Streby, Keri A</creator><creatorcontrib>Moreno, Lucas ; Teira, Pierre ; Croop, James M ; Gerber, Nicolas U ; André, Nicolas ; Aerts, Isabelle ; Gros Subias, Luis ; De Wilde, Bram ; Bautista, Francisco ; Turpin, Brian ; Kunduri, Srinivasa ; Hamidi, Ali ; Lawrence, Tatiana ; Streby, Keri A</creatorcontrib><description>The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors.
T-VEC was delivered by intralesional injection at 10
plaque-forming units (PFU)/ml on the first day, followed by 10
PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
Fifteen patients were enrolled into two cohorts based on age: cohort A1 (
= 13) 12 to ≤21 years old (soft-tissue sarcoma,
= 7; bone sarcoma,
= 3; neuroblastoma,
= 1; nasopharyngeal carcinoma,
= 1; and melanoma,
= 1) and cohort B1 (
= 2) 2 to <12 years old (melanoma,
= 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response.
T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed.
ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845.</description><identifier>ISSN: 2296-2360</identifier><identifier>EISSN: 2296-2360</identifier><identifier>DOI: 10.3389/fped.2023.1183295</identifier><identifier>PMID: 37292376</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>immunotherapy ; non-CNS tumors ; oncolytic herpes virus ; pediatric solid tumor ; Pediatrics ; relapsed and refractory cancer ; talimogene laherparepvec</subject><ispartof>Frontiers in pediatrics, 2023-05, Vol.11, p.1183295-1183295</ispartof><rights>2023 Moreno, Teira, Croop, Gerber, André, Aerts, Gros Subias, De Wilde, Bautista, Turpin, Kunduri, Hamidi, Lawrence and Streby.</rights><rights>2023 Moreno, Teira, Croop, Gerber, André, Aerts, Gros Subias, De Wilde, Bautista, Turpin, Kunduri, Hamidi, Lawrence and Streby. 2023 Moreno, Teira, Croop, Gerber, André, Aerts, Gros Subias, De Wilde, Bautista, Turpin, Kunduri, Hamidi, Lawrence and Streby</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3</citedby><cites>FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244735/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244735/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37292376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moreno, Lucas</creatorcontrib><creatorcontrib>Teira, Pierre</creatorcontrib><creatorcontrib>Croop, James M</creatorcontrib><creatorcontrib>Gerber, Nicolas U</creatorcontrib><creatorcontrib>André, Nicolas</creatorcontrib><creatorcontrib>Aerts, Isabelle</creatorcontrib><creatorcontrib>Gros Subias, Luis</creatorcontrib><creatorcontrib>De Wilde, Bram</creatorcontrib><creatorcontrib>Bautista, Francisco</creatorcontrib><creatorcontrib>Turpin, Brian</creatorcontrib><creatorcontrib>Kunduri, Srinivasa</creatorcontrib><creatorcontrib>Hamidi, Ali</creatorcontrib><creatorcontrib>Lawrence, Tatiana</creatorcontrib><creatorcontrib>Streby, Keri A</creatorcontrib><title>A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors</title><title>Frontiers in pediatrics</title><addtitle>Front Pediatr</addtitle><description>The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors.
T-VEC was delivered by intralesional injection at 10
plaque-forming units (PFU)/ml on the first day, followed by 10
PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
Fifteen patients were enrolled into two cohorts based on age: cohort A1 (
= 13) 12 to ≤21 years old (soft-tissue sarcoma,
= 7; bone sarcoma,
= 3; neuroblastoma,
= 1; nasopharyngeal carcinoma,
= 1; and melanoma,
= 1) and cohort B1 (
= 2) 2 to <12 years old (melanoma,
= 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response.
T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed.
ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845.</description><subject>immunotherapy</subject><subject>non-CNS tumors</subject><subject>oncolytic herpes virus</subject><subject>pediatric solid tumor</subject><subject>Pediatrics</subject><subject>relapsed and refractory cancer</subject><subject>talimogene laherparepvec</subject><issn>2296-2360</issn><issn>2296-2360</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkk1v3CAQhq2qVROl-QG9VBx7iDcG_AGnKor6ESlSL-0ZjWFYE2HjAt5q_1l_Xr3ZTZRwGTQz7zMMeoviI602nAt5bWc0G1YxvqFUcCabN8U5Y7ItGW-rty_uZ8VlSg_VemRXNbR5X5zxjknGu_a8-HdD5gESEnpFrIspl24q9eC8uSLj4rPTOGWMJOXF7EkOBHfgF8hI8oAkgcW8JzAZgtY6DXpPgn0shUkHv1_1ZMA4YyI7F5dEMng3hi1OSDwcKhBx3qEmbiLrQg5yXCUzZLfOTeSvywMBs4NJoyEpeGdIXsYQ04finQWf8PIUL4rf377-uv1R3v_8fnd7c1_qum1zyYBJzU2LTS-l6U1v6wZbsFxTyoSQTHcSG8kqYVpZy1YYbmttrWyQdUL3_KK4O3JNgAc1RzdC3KsATj0mQtwqiOuaHpVlAihrKi16WrcSRd0IbXknDKNc8HplfTmy5qUf0Ry-NoJ_BX1dmdygtmGnaMXquuPNSvh8IsTwZ8GU1eiSRu9hwrAkxQSrWyHWsLbSY6uOIaWI9nkOrdTBQergIHVwkDo5aNV8evnAZ8WTX_h_vGXG3A</recordid><startdate>20230524</startdate><enddate>20230524</enddate><creator>Moreno, Lucas</creator><creator>Teira, Pierre</creator><creator>Croop, James M</creator><creator>Gerber, Nicolas U</creator><creator>André, Nicolas</creator><creator>Aerts, Isabelle</creator><creator>Gros Subias, Luis</creator><creator>De Wilde, Bram</creator><creator>Bautista, Francisco</creator><creator>Turpin, Brian</creator><creator>Kunduri, Srinivasa</creator><creator>Hamidi, Ali</creator><creator>Lawrence, Tatiana</creator><creator>Streby, Keri A</creator><general>Frontiers Media S.A</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20230524</creationdate><title>A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors</title><author>Moreno, Lucas ; Teira, Pierre ; Croop, James M ; Gerber, Nicolas U ; André, Nicolas ; Aerts, Isabelle ; Gros Subias, Luis ; De Wilde, Bram ; Bautista, Francisco ; Turpin, Brian ; Kunduri, Srinivasa ; Hamidi, Ali ; Lawrence, Tatiana ; Streby, Keri A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>immunotherapy</topic><topic>non-CNS tumors</topic><topic>oncolytic herpes virus</topic><topic>pediatric solid tumor</topic><topic>Pediatrics</topic><topic>relapsed and refractory cancer</topic><topic>talimogene laherparepvec</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moreno, Lucas</creatorcontrib><creatorcontrib>Teira, Pierre</creatorcontrib><creatorcontrib>Croop, James M</creatorcontrib><creatorcontrib>Gerber, Nicolas U</creatorcontrib><creatorcontrib>André, Nicolas</creatorcontrib><creatorcontrib>Aerts, Isabelle</creatorcontrib><creatorcontrib>Gros Subias, Luis</creatorcontrib><creatorcontrib>De Wilde, Bram</creatorcontrib><creatorcontrib>Bautista, Francisco</creatorcontrib><creatorcontrib>Turpin, Brian</creatorcontrib><creatorcontrib>Kunduri, Srinivasa</creatorcontrib><creatorcontrib>Hamidi, Ali</creatorcontrib><creatorcontrib>Lawrence, Tatiana</creatorcontrib><creatorcontrib>Streby, Keri A</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moreno, Lucas</au><au>Teira, Pierre</au><au>Croop, James M</au><au>Gerber, Nicolas U</au><au>André, Nicolas</au><au>Aerts, Isabelle</au><au>Gros Subias, Luis</au><au>De Wilde, Bram</au><au>Bautista, Francisco</au><au>Turpin, Brian</au><au>Kunduri, Srinivasa</au><au>Hamidi, Ali</au><au>Lawrence, Tatiana</au><au>Streby, Keri A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors</atitle><jtitle>Frontiers in pediatrics</jtitle><addtitle>Front Pediatr</addtitle><date>2023-05-24</date><risdate>2023</risdate><volume>11</volume><spage>1183295</spage><epage>1183295</epage><pages>1183295-1183295</pages><issn>2296-2360</issn><eissn>2296-2360</eissn><abstract>The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors.
T-VEC was delivered by intralesional injection at 10
plaque-forming units (PFU)/ml on the first day, followed by 10
PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST).
Fifteen patients were enrolled into two cohorts based on age: cohort A1 (
= 13) 12 to ≤21 years old (soft-tissue sarcoma,
= 7; bone sarcoma,
= 3; neuroblastoma,
= 1; nasopharyngeal carcinoma,
= 1; and melanoma,
= 1) and cohort B1 (
= 2) 2 to <12 years old (melanoma,
= 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response.
T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed.
ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>37292376</pmid><doi>10.3389/fped.2023.1183295</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2296-2360 |
| ispartof | Frontiers in pediatrics, 2023-05, Vol.11, p.1183295-1183295 |
| issn | 2296-2360 2296-2360 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_f28a1250c8b1469e8458cf378d213834 |
| source | Open Access: PubMed Central |
| subjects | immunotherapy non-CNS tumors oncolytic herpes virus pediatric solid tumor Pediatrics relapsed and refractory cancer talimogene laherparepvec |
| title | A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T01%3A05%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20phase%201,%20first-in-child,%20multicenter%20study%20to%20evaluate%20the%20safety%20and%20efficacy%20of%20the%20oncolytic%20herpes%20virus%20talimogene%20laherparepvec%20in%20pediatric%20patients%20with%20advanced%20solid%20tumors&rft.jtitle=Frontiers%20in%20pediatrics&rft.au=Moreno,%20Lucas&rft.date=2023-05-24&rft.volume=11&rft.spage=1183295&rft.epage=1183295&rft.pages=1183295-1183295&rft.issn=2296-2360&rft.eissn=2296-2360&rft_id=info:doi/10.3389/fped.2023.1183295&rft_dat=%3Cproquest_doaj_%3E2824688282%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c466t-2a29c3d6e5b99dbdbf45e6af3c1128892c79e59208d694968d3f4cff95e278cb3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2824688282&rft_id=info:pmid/37292376&rfr_iscdi=true |