640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer

BackgroundCOM701, a novel, first in-class immune checkpoint inhibitor, anti-PVRIG, that leads to activation of T-cells. PVRL2, the ligand of PVRIG, is highly expressed in breast cancer. We have reported preliminary antitumor activity with objective responses [partial responses and a complete respons...

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Published in:Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A732-A732
Main Authors: Dumbrava, Ecaterina, Chmielowski, Bartosz, Shepard, Dale, Vaena, Daniel, Rasco, Drew, Sharma, Manish, Hamilton, Erika, Papadopoulos, Kyriakos P, Wang, Judy S, Ophir, Eran, Ferre, Pierre, Barbiro, Inbal, Cojocaru, Gady, Adewoye, Adeboye H, Patel, Manish
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Breast cancer
Cancer therapies
Clinical trials
Endometrial cancer
Immunotherapy
Metastasis
Monoclonal antibodies
Patients
Regular and Young Investigator Award Abstracts
Targeted cancer therapy
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container_end_page A732
container_issue Suppl 1
container_start_page A732
container_title Journal for immunotherapy of cancer
container_volume 11
creator Dumbrava, Ecaterina
Chmielowski, Bartosz
Shepard, Dale
Vaena, Daniel
Rasco, Drew
Sharma, Manish
Hamilton, Erika
Papadopoulos, Kyriakos P
Wang, Judy S
Ophir, Eran
Ferre, Pierre
Barbiro, Inbal
Cojocaru, Gady
Adewoye, Adeboye H
Patel, Manish
description BackgroundCOM701, a novel, first in-class immune checkpoint inhibitor, anti-PVRIG, that leads to activation of T-cells. PVRL2, the ligand of PVRIG, is highly expressed in breast cancer. We have reported preliminary antitumor activity with objective responses [partial responses and a complete response] in patients with solid tumors (MSS-CRC, platinum resistant OVCA, anal squamous CA, MSS-endometrial cancer] who received COM701 +/- nivolumab + BMS-986207 (anti-TIGIT antibody).1 2 We present results from the dose expansion cohort with COM701 + nivolumab in patients with metastatic breast cancer (MBC) (NCT03667716).MethodsWe enrolled 17 patients with MBC, all received COM701 20 mg/kg + nivolumab 480 mg, both IV Q4 weeks. Primary objectives were to determine safety and tolerability and secondary objective was to evaluate preliminary antitumor activity. Key inclusion criteria: Age ≥ 18 years, histologically confirmed locally advanced or MBC (regardless of ER/PR and HER2 status) with measurable disease, who exhausted all available standard treatments. Prior treatment with anti-PD-(L)-1, anti-CTLA-4 ICI was permissible. Key exclusion criteria: history of immune-related events that to immunotherapy treatment discontinuation, history of pneumonitis. Safety was evaluated per CTCAE v4.03 and investigator responses per RECIST v1.1.ResultsTreatment related adverse events reported in 12/17 (71%) patients, the majority [11/12 pts] were ≤G2, the most frequent was diarrhoea in 3 pts (all G1). One patient with G3 TRAE of pneumonitis (recovered), no ≥G4 TRAEs. Tumor assessments (by site): PD-L1 negative 9/17 (53%), positive/present 2/17 (12%), missing/not assessed 6/17 (35%); TMB low (
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fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_363ff12d124c4f2cbb2ae653c202e261</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_363ff12d124c4f2cbb2ae653c202e261</doaj_id><sourcerecordid>2886729996</sourcerecordid><originalsourceid>FETCH-LOGICAL-b1870-19509e859780e131c36195903488612c52d367f0b5535c042fdd163554bfdd443</originalsourceid><addsrcrecordid>eNpFkc1O3DAUhSOkSkWUZ8ASSxR6r_-SLNGopSNRsWBYW7bjFEcTe-p4qNjBghflSeowrVj56Oj46Oh-VXWGcInI5NfRZ1tToKy-W29Wi7gEyeGoOqYgsEZO5efqdJ5HAEBgrG3b4-qlJN6eXzcPjtg4GR909jGQOJDV7c8GkFyQ4B_jdj9pQ3o3xTDnpLObyS65rZ_Kh_REdMg-76eYiLbZP_r8RHwgu9LlQp7JH58fyOSynnOxLDHJFUmsDtalL9WnQW9nd_rvPanuv3_brH7UN7fX69XVTW2wbaDGTkDnWtE1LThkaJksVgeMt61EagXtmWwGMEIwYYHToe9RMiG4KYpzdlKtD7191KPaJT-V5Spqr96NmH4pncq6rVNMsmFA2iPllg_UGkO1k4LZclRHJZau80PXLsXfezdnNcZ9CmW-omVOQ7uukyXFDikzjR8BBLXgUgsutVBS_3GpBRf7C_DUi4U</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2886729996</pqid></control><display><type>article</type><title>640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer</title><source>BMJ Open Access Journals</source><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Dumbrava, Ecaterina ; Chmielowski, Bartosz ; Shepard, Dale ; Vaena, Daniel ; Rasco, Drew ; Sharma, Manish ; Hamilton, Erika ; Papadopoulos, Kyriakos P ; Wang, Judy S ; Ophir, Eran ; Ferre, Pierre ; Barbiro, Inbal ; Cojocaru, Gady ; Adewoye, Adeboye H ; Patel, Manish</creator><creatorcontrib>Dumbrava, Ecaterina ; Chmielowski, Bartosz ; Shepard, Dale ; Vaena, Daniel ; Rasco, Drew ; Sharma, Manish ; Hamilton, Erika ; Papadopoulos, Kyriakos P ; Wang, Judy S ; Ophir, Eran ; Ferre, Pierre ; Barbiro, Inbal ; Cojocaru, Gady ; Adewoye, Adeboye H ; Patel, Manish</creatorcontrib><description>BackgroundCOM701, a novel, first in-class immune checkpoint inhibitor, anti-PVRIG, that leads to activation of T-cells. PVRL2, the ligand of PVRIG, is highly expressed in breast cancer. We have reported preliminary antitumor activity with objective responses [partial responses and a complete response] in patients with solid tumors (MSS-CRC, platinum resistant OVCA, anal squamous CA, MSS-endometrial cancer] who received COM701 +/- nivolumab + BMS-986207 (anti-TIGIT antibody).1 2 We present results from the dose expansion cohort with COM701 + nivolumab in patients with metastatic breast cancer (MBC) (NCT03667716).MethodsWe enrolled 17 patients with MBC, all received COM701 20 mg/kg + nivolumab 480 mg, both IV Q4 weeks. Primary objectives were to determine safety and tolerability and secondary objective was to evaluate preliminary antitumor activity. Key inclusion criteria: Age ≥ 18 years, histologically confirmed locally advanced or MBC (regardless of ER/PR and HER2 status) with measurable disease, who exhausted all available standard treatments. Prior treatment with anti-PD-(L)-1, anti-CTLA-4 ICI was permissible. Key exclusion criteria: history of immune-related events that to immunotherapy treatment discontinuation, history of pneumonitis. Safety was evaluated per CTCAE v4.03 and investigator responses per RECIST v1.1.ResultsTreatment related adverse events reported in 12/17 (71%) patients, the majority [11/12 pts] were ≤G2, the most frequent was diarrhoea in 3 pts (all G1). One patient with G3 TRAE of pneumonitis (recovered), no ≥G4 TRAEs. Tumor assessments (by site): PD-L1 negative 9/17 (53%), positive/present 2/17 (12%), missing/not assessed 6/17 (35%); TMB low (&lt;10 mut/MB) in 10/17 (59%), missing/not assessed 7/17 (41%). Objective response rate 2/17 patients (12%) - a CR was achieved in a patient with ER+/PR-, HER2- invasive ductal carcinoma (pretreatment: PD-L1 CPS 3, PVRL2 tumor H-score 300 (both by sponsor assessment), TMB-low (5 Mut/Mb)] who received 3 prior lines of therapy and continues the study treatment (567 days). Another patient with TNBC, PD-L1 negative, TMB-low (1 Mut/Mb), with 4 prior lines of therapy with a PR remained on study treatment (296 days), 3 pts with stable disease, all PDL1 CPS&lt;1 and low TMB. Disease control rate [CR+PR+SD] 5/17 (29%). Patients with clinical benefit and serum samples available showed increased IFNg at Cycle 2–3 compared to baseline.ConclusionsThe combination is well tolerated with no dose-limiting toxicity. Encouraging preliminary antitumor activity with PR and CR reported in heavily pretreated patients with TMB-low MBC. Additional clinical and translational data will be presented at the conference. Data extract 06/09/2023.AcknowledgementsWe thank the patients for participating in this clinical trial and their families, the investigators and their staff at the clinical trial sites; Study Sponsor Compugen Ltd in collaboration with Bristol Myers Squibb; Danae Hudson, Amanda Harp, Compugen USA Inc for clinical operations oversight of the studyTrial RegistrationNCT03667716.References1. Moroney JA, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022);16 (suppl_1): 100104–100104. 10.1016/iotech/iotech1001042. Drew Rasco, Ecaterina Dumbrava et al. COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases. Journal for Immunotherapy of Cancer Nov 2022;10 (Suppl 2) A690; DOI: 10.1136/jitc-2022-SITC2022.0659Ethics ApprovalThe study obtained ethics approval from the IRBs below:1. IntegReview SSU001665542. Salus IRB IRB000130273. WIRB 201818584. IRB at Cleveland Clinic IRB#19–2385. IRB University of Chicago IRB18–08066. OHRS at Dana Farber Institute 18–5557. Columbia University IRB IRB-AAAR99988. UCLA OHRPP IRB#18–0013839. IRB of MD Anderson 2018–089110. Salus IRB IRB0001302711. Advarra Pro00052320All participants gave informed consent before taking part.</description><identifier>EISSN: 2051-1426</identifier><identifier>DOI: 10.1136/jitc-2023-SITC2023.0640</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd</publisher><subject>Breast cancer ; Cancer therapies ; Clinical trials ; Endometrial cancer ; Immunotherapy ; Metastasis ; Monoclonal antibodies ; Patients ; Regular and Young Investigator Award Abstracts ; Targeted cancer therapy</subject><ispartof>Journal for immunotherapy of cancer, 2023-11, Vol.11 (Suppl 1), p.A732-A732</ispartof><rights>Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2023 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jitc.bmj.com/content/11/Suppl_1/A732.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://jitc.bmj.com/content/11/Suppl_1/A732.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,27903,27904,36991,55328,77406,77432</link.rule.ids></links><search><creatorcontrib>Dumbrava, Ecaterina</creatorcontrib><creatorcontrib>Chmielowski, Bartosz</creatorcontrib><creatorcontrib>Shepard, Dale</creatorcontrib><creatorcontrib>Vaena, Daniel</creatorcontrib><creatorcontrib>Rasco, Drew</creatorcontrib><creatorcontrib>Sharma, Manish</creatorcontrib><creatorcontrib>Hamilton, Erika</creatorcontrib><creatorcontrib>Papadopoulos, Kyriakos P</creatorcontrib><creatorcontrib>Wang, Judy S</creatorcontrib><creatorcontrib>Ophir, Eran</creatorcontrib><creatorcontrib>Ferre, Pierre</creatorcontrib><creatorcontrib>Barbiro, Inbal</creatorcontrib><creatorcontrib>Cojocaru, Gady</creatorcontrib><creatorcontrib>Adewoye, Adeboye H</creatorcontrib><creatorcontrib>Patel, Manish</creatorcontrib><title>640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer</title><title>Journal for immunotherapy of cancer</title><addtitle>J Immunother Cancer</addtitle><description>BackgroundCOM701, a novel, first in-class immune checkpoint inhibitor, anti-PVRIG, that leads to activation of T-cells. PVRL2, the ligand of PVRIG, is highly expressed in breast cancer. We have reported preliminary antitumor activity with objective responses [partial responses and a complete response] in patients with solid tumors (MSS-CRC, platinum resistant OVCA, anal squamous CA, MSS-endometrial cancer] who received COM701 +/- nivolumab + BMS-986207 (anti-TIGIT antibody).1 2 We present results from the dose expansion cohort with COM701 + nivolumab in patients with metastatic breast cancer (MBC) (NCT03667716).MethodsWe enrolled 17 patients with MBC, all received COM701 20 mg/kg + nivolumab 480 mg, both IV Q4 weeks. Primary objectives were to determine safety and tolerability and secondary objective was to evaluate preliminary antitumor activity. Key inclusion criteria: Age ≥ 18 years, histologically confirmed locally advanced or MBC (regardless of ER/PR and HER2 status) with measurable disease, who exhausted all available standard treatments. Prior treatment with anti-PD-(L)-1, anti-CTLA-4 ICI was permissible. Key exclusion criteria: history of immune-related events that to immunotherapy treatment discontinuation, history of pneumonitis. Safety was evaluated per CTCAE v4.03 and investigator responses per RECIST v1.1.ResultsTreatment related adverse events reported in 12/17 (71%) patients, the majority [11/12 pts] were ≤G2, the most frequent was diarrhoea in 3 pts (all G1). One patient with G3 TRAE of pneumonitis (recovered), no ≥G4 TRAEs. Tumor assessments (by site): PD-L1 negative 9/17 (53%), positive/present 2/17 (12%), missing/not assessed 6/17 (35%); TMB low (&lt;10 mut/MB) in 10/17 (59%), missing/not assessed 7/17 (41%). Objective response rate 2/17 patients (12%) - a CR was achieved in a patient with ER+/PR-, HER2- invasive ductal carcinoma (pretreatment: PD-L1 CPS 3, PVRL2 tumor H-score 300 (both by sponsor assessment), TMB-low (5 Mut/Mb)] who received 3 prior lines of therapy and continues the study treatment (567 days). Another patient with TNBC, PD-L1 negative, TMB-low (1 Mut/Mb), with 4 prior lines of therapy with a PR remained on study treatment (296 days), 3 pts with stable disease, all PDL1 CPS&lt;1 and low TMB. Disease control rate [CR+PR+SD] 5/17 (29%). Patients with clinical benefit and serum samples available showed increased IFNg at Cycle 2–3 compared to baseline.ConclusionsThe combination is well tolerated with no dose-limiting toxicity. Encouraging preliminary antitumor activity with PR and CR reported in heavily pretreated patients with TMB-low MBC. Additional clinical and translational data will be presented at the conference. Data extract 06/09/2023.AcknowledgementsWe thank the patients for participating in this clinical trial and their families, the investigators and their staff at the clinical trial sites; Study Sponsor Compugen Ltd in collaboration with Bristol Myers Squibb; Danae Hudson, Amanda Harp, Compugen USA Inc for clinical operations oversight of the studyTrial RegistrationNCT03667716.References1. Moroney JA, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022);16 (suppl_1): 100104–100104. 10.1016/iotech/iotech1001042. Drew Rasco, Ecaterina Dumbrava et al. COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases. Journal for Immunotherapy of Cancer Nov 2022;10 (Suppl 2) A690; DOI: 10.1136/jitc-2022-SITC2022.0659Ethics ApprovalThe study obtained ethics approval from the IRBs below:1. IntegReview SSU001665542. Salus IRB IRB000130273. WIRB 201818584. IRB at Cleveland Clinic IRB#19–2385. IRB University of Chicago IRB18–08066. OHRS at Dana Farber Institute 18–5557. Columbia University IRB IRB-AAAR99988. UCLA OHRPP IRB#18–0013839. IRB of MD Anderson 2018–089110. Salus IRB IRB0001302711. Advarra Pro00052320All participants gave informed consent before taking part.</description><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Clinical trials</subject><subject>Endometrial cancer</subject><subject>Immunotherapy</subject><subject>Metastasis</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Regular and Young Investigator Award Abstracts</subject><subject>Targeted cancer therapy</subject><issn>2051-1426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>DOA</sourceid><recordid>eNpFkc1O3DAUhSOkSkWUZ8ASSxR6r_-SLNGopSNRsWBYW7bjFEcTe-p4qNjBghflSeowrVj56Oj46Oh-VXWGcInI5NfRZ1tToKy-W29Wi7gEyeGoOqYgsEZO5efqdJ5HAEBgrG3b4-qlJN6eXzcPjtg4GR909jGQOJDV7c8GkFyQ4B_jdj9pQ3o3xTDnpLObyS65rZ_Kh_REdMg-76eYiLbZP_r8RHwgu9LlQp7JH58fyOSynnOxLDHJFUmsDtalL9WnQW9nd_rvPanuv3_brH7UN7fX69XVTW2wbaDGTkDnWtE1LThkaJksVgeMt61EagXtmWwGMEIwYYHToe9RMiG4KYpzdlKtD7191KPaJT-V5Spqr96NmH4pncq6rVNMsmFA2iPllg_UGkO1k4LZclRHJZau80PXLsXfezdnNcZ9CmW-omVOQ7uukyXFDikzjR8BBLXgUgsutVBS_3GpBRf7C_DUi4U</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>Dumbrava, Ecaterina</creator><creator>Chmielowski, Bartosz</creator><creator>Shepard, Dale</creator><creator>Vaena, Daniel</creator><creator>Rasco, Drew</creator><creator>Sharma, Manish</creator><creator>Hamilton, Erika</creator><creator>Papadopoulos, Kyriakos P</creator><creator>Wang, Judy S</creator><creator>Ophir, Eran</creator><creator>Ferre, Pierre</creator><creator>Barbiro, Inbal</creator><creator>Cojocaru, Gady</creator><creator>Adewoye, Adeboye H</creator><creator>Patel, Manish</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>K9.</scope><scope>DOA</scope></search><sort><creationdate>20231101</creationdate><title>640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer</title><author>Dumbrava, Ecaterina ; Chmielowski, Bartosz ; Shepard, Dale ; Vaena, Daniel ; Rasco, Drew ; Sharma, Manish ; Hamilton, Erika ; Papadopoulos, Kyriakos P ; Wang, Judy S ; Ophir, Eran ; Ferre, Pierre ; Barbiro, Inbal ; Cojocaru, Gady ; Adewoye, Adeboye H ; Patel, Manish</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1870-19509e859780e131c36195903488612c52d367f0b5535c042fdd163554bfdd443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Clinical trials</topic><topic>Endometrial cancer</topic><topic>Immunotherapy</topic><topic>Metastasis</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Regular and Young Investigator Award Abstracts</topic><topic>Targeted cancer therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dumbrava, Ecaterina</creatorcontrib><creatorcontrib>Chmielowski, Bartosz</creatorcontrib><creatorcontrib>Shepard, Dale</creatorcontrib><creatorcontrib>Vaena, Daniel</creatorcontrib><creatorcontrib>Rasco, Drew</creatorcontrib><creatorcontrib>Sharma, Manish</creatorcontrib><creatorcontrib>Hamilton, Erika</creatorcontrib><creatorcontrib>Papadopoulos, Kyriakos P</creatorcontrib><creatorcontrib>Wang, Judy S</creatorcontrib><creatorcontrib>Ophir, Eran</creatorcontrib><creatorcontrib>Ferre, Pierre</creatorcontrib><creatorcontrib>Barbiro, Inbal</creatorcontrib><creatorcontrib>Cojocaru, Gady</creatorcontrib><creatorcontrib>Adewoye, Adeboye H</creatorcontrib><creatorcontrib>Patel, Manish</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Directory of Open Access Journals</collection><jtitle>Journal for immunotherapy of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dumbrava, Ecaterina</au><au>Chmielowski, Bartosz</au><au>Shepard, Dale</au><au>Vaena, Daniel</au><au>Rasco, Drew</au><au>Sharma, Manish</au><au>Hamilton, Erika</au><au>Papadopoulos, Kyriakos P</au><au>Wang, Judy S</au><au>Ophir, Eran</au><au>Ferre, Pierre</au><au>Barbiro, Inbal</au><au>Cojocaru, Gady</au><au>Adewoye, Adeboye H</au><au>Patel, Manish</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer</atitle><jtitle>Journal for immunotherapy of cancer</jtitle><stitle>J Immunother Cancer</stitle><date>2023-11-01</date><risdate>2023</risdate><volume>11</volume><issue>Suppl 1</issue><spage>A732</spage><epage>A732</epage><pages>A732-A732</pages><eissn>2051-1426</eissn><abstract>BackgroundCOM701, a novel, first in-class immune checkpoint inhibitor, anti-PVRIG, that leads to activation of T-cells. PVRL2, the ligand of PVRIG, is highly expressed in breast cancer. We have reported preliminary antitumor activity with objective responses [partial responses and a complete response] in patients with solid tumors (MSS-CRC, platinum resistant OVCA, anal squamous CA, MSS-endometrial cancer] who received COM701 +/- nivolumab + BMS-986207 (anti-TIGIT antibody).1 2 We present results from the dose expansion cohort with COM701 + nivolumab in patients with metastatic breast cancer (MBC) (NCT03667716).MethodsWe enrolled 17 patients with MBC, all received COM701 20 mg/kg + nivolumab 480 mg, both IV Q4 weeks. Primary objectives were to determine safety and tolerability and secondary objective was to evaluate preliminary antitumor activity. Key inclusion criteria: Age ≥ 18 years, histologically confirmed locally advanced or MBC (regardless of ER/PR and HER2 status) with measurable disease, who exhausted all available standard treatments. Prior treatment with anti-PD-(L)-1, anti-CTLA-4 ICI was permissible. Key exclusion criteria: history of immune-related events that to immunotherapy treatment discontinuation, history of pneumonitis. Safety was evaluated per CTCAE v4.03 and investigator responses per RECIST v1.1.ResultsTreatment related adverse events reported in 12/17 (71%) patients, the majority [11/12 pts] were ≤G2, the most frequent was diarrhoea in 3 pts (all G1). One patient with G3 TRAE of pneumonitis (recovered), no ≥G4 TRAEs. Tumor assessments (by site): PD-L1 negative 9/17 (53%), positive/present 2/17 (12%), missing/not assessed 6/17 (35%); TMB low (&lt;10 mut/MB) in 10/17 (59%), missing/not assessed 7/17 (41%). Objective response rate 2/17 patients (12%) - a CR was achieved in a patient with ER+/PR-, HER2- invasive ductal carcinoma (pretreatment: PD-L1 CPS 3, PVRL2 tumor H-score 300 (both by sponsor assessment), TMB-low (5 Mut/Mb)] who received 3 prior lines of therapy and continues the study treatment (567 days). Another patient with TNBC, PD-L1 negative, TMB-low (1 Mut/Mb), with 4 prior lines of therapy with a PR remained on study treatment (296 days), 3 pts with stable disease, all PDL1 CPS&lt;1 and low TMB. Disease control rate [CR+PR+SD] 5/17 (29%). Patients with clinical benefit and serum samples available showed increased IFNg at Cycle 2–3 compared to baseline.ConclusionsThe combination is well tolerated with no dose-limiting toxicity. Encouraging preliminary antitumor activity with PR and CR reported in heavily pretreated patients with TMB-low MBC. Additional clinical and translational data will be presented at the conference. Data extract 06/09/2023.AcknowledgementsWe thank the patients for participating in this clinical trial and their families, the investigators and their staff at the clinical trial sites; Study Sponsor Compugen Ltd in collaboration with Bristol Myers Squibb; Danae Hudson, Amanda Harp, Compugen USA Inc for clinical operations oversight of the studyTrial RegistrationNCT03667716.References1. Moroney JA, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022);16 (suppl_1): 100104–100104. 10.1016/iotech/iotech1001042. Drew Rasco, Ecaterina Dumbrava et al. COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases. Journal for Immunotherapy of Cancer Nov 2022;10 (Suppl 2) A690; DOI: 10.1136/jitc-2022-SITC2022.0659Ethics ApprovalThe study obtained ethics approval from the IRBs below:1. IntegReview SSU001665542. Salus IRB IRB000130273. WIRB 201818584. IRB at Cleveland Clinic IRB#19–2385. IRB University of Chicago IRB18–08066. OHRS at Dana Farber Institute 18–5557. Columbia University IRB IRB-AAAR99988. UCLA OHRPP IRB#18–0013839. IRB of MD Anderson 2018–089110. Salus IRB IRB0001302711. Advarra Pro00052320All participants gave informed consent before taking part.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd</pub><doi>10.1136/jitc-2023-SITC2023.0640</doi><oa>free_for_read</oa></addata></record>
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subjects Breast cancer
Cancer therapies
Clinical trials
Endometrial cancer
Immunotherapy
Metastasis
Monoclonal antibodies
Patients
Regular and Young Investigator Award Abstracts
Targeted cancer therapy
title 640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer
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