Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1) : an international, open-label, phase 2 trial
Copyright © 2024 Elsevier Ltd. All rights reserved..
BACKGROUND: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.
METHODS: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 109-10·0 × 109 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3.
FINDINGS: Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4-36·1). Overall response rate was 37% (19 of 52; 95% CI 24-51) overall, 39% (17 of 44; 24-55) for patients with synovial sarcoma, and 25% (two of eight; 3-65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred.
INTERPRETATION: Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies.
FUNDING: Adaptimmune.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:403 |
---|---|
Enthalten in: |
Lancet (London, England) - 403(2024), 10435 vom: 13. Apr., Seite 1460-1471 |
Sprache: |
Englisch |
---|
Links: |
---|
Themen: |
Clinical Trial, Phase II |
---|
Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT04044768 Citation Status MEDLINE |
---|
doi: |
10.1016/S0140-6736(24)00319-2 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM370442490 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM370442490 | ||
003 | DE-627 | ||
005 | 20240415233617.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240331s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/S0140-6736(24)00319-2 |2 doi | |
028 | 5 | 2 | |a pubmed24n1376.xml |
035 | |a (DE-627)NLM370442490 | ||
035 | |a (NLM)38554725 | ||
035 | |a (PII)S0140-6736(24)00319-2 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a D'Angelo, Sandra P |e verfasserin |4 aut | |
245 | 1 | 0 | |a Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1) |b an international, open-label, phase 2 trial |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 15.04.2024 | ||
500 | |a Date Revised 15.04.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a ClinicalTrials.gov: NCT04044768 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
520 | |a BACKGROUND: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma | ||
520 | |a METHODS: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 109-10·0 × 109 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3 | ||
520 | |a FINDINGS: Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4-36·1). Overall response rate was 37% (19 of 52; 95% CI 24-51) overall, 39% (17 of 44; 24-55) for patients with synovial sarcoma, and 25% (two of eight; 3-65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred | ||
520 | |a INTERPRETATION: Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies | ||
520 | |a FUNDING: Adaptimmune | ||
650 | 4 | |a Clinical Trial, Phase II | |
650 | 4 | |a Journal Article | |
650 | 7 | |a Ifosfamide |2 NLM | |
650 | 7 | |a UM20QQM95Y |2 NLM | |
650 | 7 | |a HLA-A Antigens |2 NLM | |
700 | 1 | |a Araujo, Dejka M |e verfasserin |4 aut | |
700 | 1 | |a Abdul Razak, Albiruni R |e verfasserin |4 aut | |
700 | 1 | |a Agulnik, Mark |e verfasserin |4 aut | |
700 | 1 | |a Attia, Steven |e verfasserin |4 aut | |
700 | 1 | |a Blay, Jean-Yves |e verfasserin |4 aut | |
700 | 1 | |a Carrasco Garcia, Irene |e verfasserin |4 aut | |
700 | 1 | |a Charlson, John A |e verfasserin |4 aut | |
700 | 1 | |a Choy, Edwin |e verfasserin |4 aut | |
700 | 1 | |a Demetri, George D |e verfasserin |4 aut | |
700 | 1 | |a Druta, Mihaela |e verfasserin |4 aut | |
700 | 1 | |a Forcade, Edouard |e verfasserin |4 aut | |
700 | 1 | |a Ganjoo, Kristen N |e verfasserin |4 aut | |
700 | 1 | |a Glod, John |e verfasserin |4 aut | |
700 | 1 | |a Keedy, Vicki L |e verfasserin |4 aut | |
700 | 1 | |a Le Cesne, Axel |e verfasserin |4 aut | |
700 | 1 | |a Liebner, David A |e verfasserin |4 aut | |
700 | 1 | |a Moreno, Victor |e verfasserin |4 aut | |
700 | 1 | |a Pollack, Seth M |e verfasserin |4 aut | |
700 | 1 | |a Schuetze, Scott M |e verfasserin |4 aut | |
700 | 1 | |a Schwartz, Gary K |e verfasserin |4 aut | |
700 | 1 | |a Strauss, Sandra J |e verfasserin |4 aut | |
700 | 1 | |a Tap, William D |e verfasserin |4 aut | |
700 | 1 | |a Thistlethwaite, Fiona |e verfasserin |4 aut | |
700 | 1 | |a Valverde Morales, Claudia Maria |e verfasserin |4 aut | |
700 | 1 | |a Wagner, Michael J |e verfasserin |4 aut | |
700 | 1 | |a Wilky, Breelyn A |e verfasserin |4 aut | |
700 | 1 | |a McAlpine, Cheryl |e verfasserin |4 aut | |
700 | 1 | |a Hudson, Laura |e verfasserin |4 aut | |
700 | 1 | |a Navenot, Jean-Marc |e verfasserin |4 aut | |
700 | 1 | |a Wang, Tianjiao |e verfasserin |4 aut | |
700 | 1 | |a Bai, Jane |e verfasserin |4 aut | |
700 | 1 | |a Rafail, Stavros |e verfasserin |4 aut | |
700 | 1 | |a Wang, Ruoxi |e verfasserin |4 aut | |
700 | 1 | |a Sun, Amy |e verfasserin |4 aut | |
700 | 1 | |a Fernandes, Lilliam |e verfasserin |4 aut | |
700 | 1 | |a Van Winkle, Erin |e verfasserin |4 aut | |
700 | 1 | |a Elefant, Erica |e verfasserin |4 aut | |
700 | 1 | |a Lunt, Colin |e verfasserin |4 aut | |
700 | 1 | |a Norry, Elliot |e verfasserin |4 aut | |
700 | 1 | |a Williams, Dennis |e verfasserin |4 aut | |
700 | 1 | |a Biswas, Swethajit |e verfasserin |4 aut | |
700 | 1 | |a Van Tine, Brian A |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Lancet (London, England) |d 1945 |g 403(2024), 10435 vom: 13. Apr., Seite 1460-1471 |w (DE-627)NLM000473936 |x 1474-547X |7 nnns |
773 | 1 | 8 | |g volume:403 |g year:2024 |g number:10435 |g day:13 |g month:04 |g pages:1460-1471 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/S0140-6736(24)00319-2 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 403 |j 2024 |e 10435 |b 13 |c 04 |h 1460-1471 |