SITC 2021 - TACTI-002 Poster

Results from a Phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic 2nd line head and neck squamous cell carcinoma (HNSCC)

Abstract # 359

López Pousa1, E Felip2, M Forster3, B Doger4, P Roxburgh5, P Bajaj6, J A Peguero7, E Carcereny8, M Krebs9, C Mueller10, F Triebel11

1Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2Vall d' Hebron Institute of Oncology, Barcelona, Spain; 3UCL Cancer Institute / University College London Hospitals NHS Foundation, London, UK; 4 START Madrid- Fundacion Jimenez Díaz, Madrid, Spain; 5Institute of Cancer Sciences, University of Glasgow and The Beatson West of Scotland Cancer Centre, Glasgow, UK; 6Tasman Oncology, Southport, Australia; 7Oncology Consultants, P.A., Houston, Texas; 8Catalan Institute of Oncology Badalona-Hospital Germans Trias i Pujol, B-ARGO group, Badalona, Spain; 9Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK; 10 Clinical Development, Immutep GmbH, Berlin, Germany; 11Research & Development, Immutep S.A.S., Orsay, France

BACKGROUND

Figure 1. efti's mechanism of action

METHODS

Study Design and Patients

Eftilagimod alpha (efti) is a soluble LAG-3 protein binding to a subset of MHC class II molecules, thus mediating antigen presenting cell (APC) and CD8 T-cell activation (Figure 1). Such stimulation of the dendritic cell network and resulting T cell recruitment may lead to stronger anti-tumor responses in combination with pembrolizumab than observed with pembrolizumab alone. We report results from the 2nd line metastatic head and neck squamous cell carcinoma (HNSCC) cohort (Part C) of the TACTI-002 study (NCT03625323).

BASELINE CHARACTERISTICS

EFFICACY

•	A total of 39 patients were enrolled and treated into this	Figure 3. Spider plot (N=31)*
	part of the study. Baseline characteristics are reported in		100
	Table 1.
			therapy	80
Table 1. Baseline characteristics (N=39)	60
	Baseline parameters, n(%)
		of	40
	Age, median (years)	62 (37-84)	to start
	20
	Female / Male	4 (10.3) / 35 (89.7)			
	ECOG 0 / 1	13 (33.3) / 26 (66.7)	compared	0
	Non-smoker / Ex- or Current smoker	6 (15.4) / 33 (84.6)	-20
	Previous chemotherapy	39 (100)	-40
	change
	Previous cetuximab	16 (41.0)	-60
	Patients with lung / liver metastasis	19 (48.7) / 6 (17.6)
	%	-80
	Primary tumor location, n (%)
			-100							
	Oral cavity	12 (30.8)
		0	12	24	36	48	60	72	84	96	108
	Oropharynx	14 (35.9)

Figure 4. Waterfall plot (N=31)*

100	Best response :
		iUPD/iCPD

baseline	75																							iSD
																							iPR
50																							iCR
25
from
0														84	NE 1	100	2	70	55	50	75	25	85 40	< 5	41	PD -L1
change	10	0	0	0	11	10	NE 28	0	NE 0	41	1	49	0	NY 15												CPS
-25
%
Best	-50
																	***
	-75
	-100																						**

• ORR (IRECIST) of 35.5% in evaluable patients (Table 2).
• 5 patients (13.5%) with complete responses (Table 2).
• 5 patients still under therapy and 1 patient completed 2 years of therapy (Figure 3).
• Responses seen in PD-L1 low and high expressors (Figure 4).
• 91% of responses confirmed.
• Median duration of response not reached; all ongoing responses lasting 9+ months (Figure 5).
• ORR, 6-month PFS and 12-month OS rates for PD-L1 CPS ≥1 patients are 40.7%, 41% and 48% respectively (Table 3).
• ORR, 6-month PFS and 12-month OS rates for PD-L1 CPS ≥20 patients are 64.3%, 57.1% and 64.3%, respectively (Table 3).

Figure 5. Duration of response for confirmed responders (N=10)

• Non-randomized,multinational, open-label, trial for 2nd line, PD-X naive, PD-L1all-comer HNSCC patients.
• Simon's optimal two stage designed trial, sponsored by Immutep in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD).
• Efti is administered as a 30 mg subcutaneous injection every 2 weeks for the first 8 cycles and every 3 weeks for the following 9 cycles. Pembrolizumab is administered at a standard dose of 200 mg intravenous infusion every 3 weeks for maximum of 2 years (Figure 2).

Figure 2. Study design

Hypopharynx	7	(17.9)	Time	(weeks )
Larynx	6	(15.4)
PD-L1 CPS score, n (%)			Table 2. Best overall response (iRECIST), all comer N=37#
CPS <1	6 (15.4)	Best overall response, iRECIST	Investigator assessment
CPS 1-19	15 (38.5)	N (%)
CPS ≥20	14 (35.9)	Complete Response	5 (13.5)
CPS not evaluable or unknown	4 (10.3)	Partial Response	6 (16.2)
			Stable Disease	3 (8.1)
*… evaluable set (N=31): ≥1 treatment and ≥1 post-baseline tumor staging	Progression	17 (45.9)
Not evaluable¶	6 (16.2)
**… lymph node as target lesion
*** … disease progression despite target lesion decrease due to new lesions	Disease Control Rate	14 (37.8)
#... full analysis set (N=37): ≥1 treatment and no death due to COVID-19 prior	Overall Response Rate	11 (29.7)
to first post-baseline staging
		[95% CI]	[15.9 - 47.0]
¶ … not evaluable set (N=6): dropped off prior to first staging or were not
evaluable post-baseline for any reason			Overall Response Rate - Evaluable pts*	11 (35.5)
… still under therapy			[95% CI]	[19.2 - 54.6]
… treated beyond progression

Table 3. Response according to PD-L1 subgroup

CPS score	All comer	≥1	≥20
(N=37)	(N=27)	(n=14)
ORR (iRECIST)
ORR, %	29.7	40.7	64.3
Overall survival
No. of events	23	17	7
6-month OS, %	54.7	55.5	71.4
12-month OS, %	48.4	48.2	64.3
Progression-free survival
No. of events	30	17	8
3-month PFS, %	37.8	48.2	64.3
6-month PFS, %	32.4	40.7	57.1

	100
of Survival	50
Probability
	0
	0	10	20	30
		Time	(months)

EXPOSURE AND SAFETY

CONCLUSION

Assessments and Statistical Analyses:

• Primary Endpoint: Objective response rate (ORR), as per iRECIST.
• Secondary Endpoints: Progression free survival (PFS), overall survival
	(OS), safety and tolerability, PK/PD and exploratory biomarkers.
• Central assessment of tumor cell PD-L1 expression (by Dako PD-L1
	immunohistochemistry (IHC) 22C3 pharmDx) after enrolment.
• Imaging performed every 9 weeks and reported according to iRECIST.
•	Safety was analyzed in all patients who received at least one dose of study
	medication.
•	Efficacy was analyzed in all patients with measurable disease at baseline,
	who received at least one dose of any study medication and did not die of
	COVID-19 prior to the first post-baseline assessment.

Table 4. General overview of adverse events (N=39)

Safety parameter	N (%)
Patients with any TEAE	35 (89.7)
Patients with any SAE	18 (46.2)
thereof related to efti/pembro	2 (5.1) / 2 (5.1)
Patients with any grade ≥3 TEAE	24 (61.5)
thereof related to efti/pembro	4 (10.3) / 3 (7.7)
Patients with fatal TEAEs	7 (17.9)
thereof related to efti/pembro	0 / 0
Patients with TEAEs leading to discontinuation of efti	6 (15.4)
thereof related to efti/pembro	0 / 0
Patients with TEAEs leading to discontinuation of pembro	7 (17.9)
thereof related to efti/pembro	1 / 2.6

Table 5. Treatment-emergent adverse events occurring ≥10% (N=39)

Adverse event (PT)	Any grade N (%)	Grade 3 N (%)	Grade 4/5 N (%)
Hypothyroidism	8 (20.5)	1 (2.6)	-
Cough	7 (17.9)	-	-
Asthenia	6 (15.4)	-	-
Fatigue	5 (12.8)	-	-
Anaemia	5 (12.8)	4 (10.3)
Diarrhoea	5 (12.8)	-	-
Weight decreased	5 (12.8)	-	-
URTI	4 (10.3)	-	-
Back pain	4 (10.3)	-	-
Pain in extremity	4 (10.3)	2 (5.1)	-

• Encouraging ORR (30% according to iRECIST) in patients

unselected for PD-L1.

• 13.5% complete responses observed.

• Durable, deep responses with median DoR not yet reached and

min. duration of 9+ months.

• Trends compare favorably to KEYNOTE-040 (ORR ~15%)1 in a

comparable patient population.

• The combination of efti plus pembrolizumab is well-tolerated

with no new safety signals.

• Majority of most frequent adverse events are mild to moderate.

• Data has led to fast-track designation by the US FDA for 1st line

HNSCC, resulting in a phase IIb study comparing efti and

pembrolizumab to pembrolizumab alone in PD-L1-positive 1st

APC…antigen-presenting cell	PD-X...PD-1 or PD-L1 targeted
CI…confidence interval	therapy
ECOG…Eastern Cooperative Oncology	PFS...progression-free survival
Group	PK...pharmacokinetics
HNSCC...head & neck squamous cell	PT...preferred term
cancer	ORR…objective response rate
iRECIST…Immune Response	SAE…serious adverse event
Evaluation Criteria In Solid Tumors	TEAE…treatment-emergent adverse
LAG-3...Lymphocyte Activation gene-3	event
MHC…Major Histocompatibility	TRAE…treatment-related adverse
Complex	event
NSCLC...non-small cell lung cancer
PD...pharmacodynamics	1. Cohen E, et al. Lancet 2019; 393:
PD-L1...Programmed Death ligand-1	156-167.(KN-040)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA provided pembrolizumab for the study.

The trial identifiers are IMP321-P015 (Sponsor code), Keynote-PN798 (MSD code), 2018-001994-25 (EudraCT) and NCT03625323 (ClinicalTrials.gov).

• Database cut-off date was April 16, 2021 (safety) and August 4, 2021

(efficacy); minimum follow up for efficacy was 8+ months.

• The most common TEAEs were hypothyroidism (20.5%), cough (17.9%) and asthenia (15.4%) (Table 5).
• No treatment-related deaths occurred (Table 4).

line HNSCC patients (NCT04811027).

Corresponding author: Frederic Triebel, [e-mail]