Final results from TACTI-002 Part C: A phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with metastatic 2nd line head and neck squamous cell carcinoma unselected for PD-L1.

person Bernard Doger de Spéville Early Phase Clinical Trials Unit, START Madrid Fundacion Jimenez Diaz, Madrid, Spain info_outline Bernard Doger de Spéville, Enriqueta Felip, Martin Forster, Margarita Majem, Pawan Bajaj, Julio Antonio Peguero, Enric Carcereny, Matthew G Krebs, Uma Mukherjee, Christian Mueller, Frederic Triebel

Authors person Bernard Doger de Spéville Early Phase Clinical Trials Unit, START Madrid Fundacion Jimenez Diaz, Madrid, Spain info_outline Bernard Doger de Spéville, Enriqueta Felip, Martin Forster, Margarita Majem, Pawan Bajaj, Julio Antonio Peguero, Enric Carcereny, Matthew G Krebs, Uma Mukherjee, Christian Mueller, Frederic Triebel Organizations Early Phase Clinical Trials Unit, START Madrid Fundacion Jimenez Diaz, Madrid, Spain, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, University College London Hospital NHS Trust, London, United Kingdom, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain, Tasman Oncology, Queensland, Australia, Oncology Consultants, Houston, TX, Hospital Germans Trias i Pujol. ICO Badalona, Badalona, Spain, Christie NHS Foundation Trust, Manchester, United Kingdom, University College Hospital-London, London, United Kingdom, Clinical Development, Immutep, Berlin, Germany, IMMUTEP, Châtenay-Malabry, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Immutep S.A Background: Eftilagimod alpha (E), a soluble LAG-3 protein, acts as an MHC class II agonist triggering activation of antigen-presenting cells (APC) and CD8 T-cells. Using efti to enhance patients’ immunity may lead to stronger anti-tumor responses than observed with pembrolizumab (P) alone. We report final results from Part C of the TACTI-002 trial (NCT03625323) where 2 nd line metastatic head and neck squamous cell carcinoma (HNSCC) patients (pts) unselected for PD-L1 were treated with E + P. Methods: Pts with metastatic HNSCC, unselected for PD-L1 expression with disease progression on or after 1 st line platinum-based therapy (± cetuximab) were enrolled. Primary endpoint (EP) was objective response rate (ORR) by iRECIST. Other EPs included tolerability, progression free survival (PFS), duration of response (DoR), and overall survival (OS). Pts received E (30 mg SC Q2W for eight 3-week cycles and then Q3W up to 1 yr) with P (200 mg IV Q3W up to 2 yrs). Imaging was performed Q9W. PD-L1 was retrospectively assessed using the IHC 22C3 kit. The study was approved by ethic committees and institutional review boards. Results: 39 pts were enrolled between Mar 2019-Jan 2021 (cut-off Jul 2022) with HNSCC of oropharynx (38%), oral cavity (32%), hypopharynx (19%) and larynx (16%). Median age was 63 yrs (48-84 yrs) and 90% were male. ECOG PS was 0 and 1 in 35% and 65% of pts. Two pts were excluded from efficacy results due to fatal COVID-19 prior to their first post-baseline scan. The primary EP, ORR by iRECIST, was 30% with 14% complete responders (see table). ORR by RECIST 1.1 was comparable (24%). Median PFS by iRECIST was 2.1 mo with 32% of pts progression-free at 6 mo. Median OS was 8.7 mo with 46% alive at 12 mo. Median DoR by iRECIST was not reached with 17 mo min FU. Responses were seen in all PD-L1 subgroups (see table). ORR, 6-mo PFS, 12-mo OS rates for PD-L1 CPS ≥20 were 60%, 53%, 73% with a median OS of 15.5 months. Two pts (5%) discontinued due to adverse events (AE) (fatigue and arthralgia [each grade 2]; pneumonitis [grade 3]) that were related to study treatment (efti and/or pembro). The most common (≥15%) AEs were hypothyroidism (21%), asthenia (21%), cough (18%), anemia (18%), weight decrease (18%), and fatigue (15%). Conclusions: Efti + pembrolizumab is safe, showing encouraging antitumor activity in platinum and partially cetuximab pre-treated, 2nd line HNSCC patients. TACTI-003 (NCT04811027) a randomized study in 1st line HNSCC is currently recruiting. Response by iRECIST: Clinical trial information: NCT03625323. Overall (ITT) N=37 PD-L1 CPS ≥20 N=15 PD-L1 CPS <20 N=17 CR, n (%) PR, n (%) 5 (14) 6 (16) 4 (27) 5 (33) 1 (5.9) 1 (5.9) ORR, n (%) DCR, n (%) 11 (30) 14 (38) 9 (60) 9 (60) 2 (11.8) 4 (23.5) mPFS, mo 6-mo PFS rate, (%) mOS, mo 12-mo OS rate, (%) mDoR, mo 12-mo DoR rate, (%) 2.1 32.4 8.7 46.0 NR 80.0 13.6 53.3 15.5 66.7 NR 87.5 2.0 17.7 7.5 35.3 12.0 50.0 NR: not reached.

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