Immutep : ELCC 2022 - TACTI-002 Poster for 2nd line NSCLC

Results from a phase II study investigating eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in 2nd line PD-1/PD-L1 refractory metastatic non-small cell lung carcinoma (NSCLC) patients

Krebs M.G 1; Majem M2; Forster M3; Peguero J 4; Clay T5; Felip E6; Iams W7; Roxburgh P8; Dodger B9; Bajaj P10; Mueller C11; Triebel F12

1Krebs: Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK; 2Majem: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 3Forster: UCL Cancer Institute / University College London Hospitals NHS Foundation, London, UK; 4Peguero: Oncology Consultants, P.A., Houston, USA; 5Clay: St John of God Subiaco Hospital, Perth, Australia; 6Felip: Vall d'Hebron University Hospital, Barcelona, Spain; 7Iams: Vanderbilt Ingram Cancer Center Division of Hematology/Oncology, Tennessee, United States; 8Roxburgh: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow and Beatson West of Scotland Cancer Centre, Scotland, United Kingdom; 9Doger: Fundación Jiménez Diaz, Madrid, Spain; 10Bajaj: Tasman Oncology, Queensland, Australia; 11Mueller: Clinical Development, Immutep GmbH, Berlin, Germany; 12Triebel: Research & 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 PD-X refractory metastatic non-small cell lung carcinoma (NSCLC) cohort (Part B) of the TACTI-002 study (NCT03625323).

• • Non-randomized, multinational, open-label, phase II trial.

• • 2nd line, PD-X refractory metastatic PD-L1 all-comer NSCLC patients.

• • Simon's two stage design.

• • 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 (total 1 year). 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

Assessments and Statistical Analyses:

• • Primary Endpoint: Objective response rate (ORR), as per iRECIST.

• • Secondary Endpoints: Progression free survival (PFS) and other efficacy parameter, safety and tolerability, and exploratory biomarkers.

• • Central assessment of tumor cell PD-L1 expression (by Dako PD-L1 IHC 22C3 pharmDx) after enrolment.

• • Imaging performed every 9 weeks and reported according to iRECIST and RECIST 1.1.

• • Safety and efficacy was analyzed following intent to treat principle (all patients who received at least one dose of study medication).

• • Database cut-off date was January 21, 2022 (min. follow up of 5+ months).

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First Author COI: Matthew Krebs,[e-mail]

Honoraria - Roche, Jassen; Consulting or Advisory Role - Janssen; Roche, Bayer, Seattle Genetics; Research Funding - Roche (Inst); Travel, Accommodation, Expenses - AstraZeneca; BerGenBio; Immutep

Corresponding author: Frederic Triebel,[e-mail]

Sponsored by: Immutep S.A

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

BASELINE CHARACTERISTICS

• • A total of 36 patients were enrolled and treated into this part of the study. Baseline characteristics are reported in Table 1.

• • Majority of patients presented with PD-L1 TPS <50% (69.4%) and received prior chemotherapy in combination with PD-1/PD-L1 therapy (72.2%).

Table 1. Baseline characteristics (N=36)

Baseline parameters, n (%)
Age (years), median (range)	67 (46-84)
Female Male	14 (38.9) 22 (61.1)
ECOG 0 ECOG 1	12 (33.3) 24 (66.7)
Current or Ex-smoker Non-smoker	31 (86.1) 5 (13.9)
Squamous Non-squamous pathology Unknown	7 (19.4) 28 (77.8) 1 (2.8)
Prior PD-1/PD-L1 therapy with chemotherapy	36 (100) 26 (72.2)
Liver metastasis	4 (11.1)
Tumor resistance* Primary resistance Secondary resistance	11 (30.6) 24 (66.7)
PD-L1 (TPS) <1% 1-49% ≥50% Not evaluable/not yet	13 (36.1) 12 (33.3) 7 (19.4) 4 (11.1)

*... Tumor resistance defined according to SITC Immunotherapy Resistance Taskforce consensus1

References:

• 1 Kluger HM et al, J Immunotherapy Cancer. 2020

  Mar;8(1):e000398. doi: 10.1136/jitc-2019-000398

• 2 Saâda-Bouzid E et al, Ann Oncol. 2017 Jul 1;28(7):1605-1611.

  doi: 10.1093/annonc/mdx178

EXPOSURE AND SAFETY

EFFICACY

• • ORR (iRECIST) of 6% in the intent to treat population(Table 2).

• • Both responders showed deep (Figure 4) and durable partial responses (Figure 3).

• • 36 % disease control rate and 26% being progression free at 6 months

• • Comparable results using RECIST 1.1.

• • 6 patients still under therapy (Figure 3) and 73% alive at 6 months.

Figure 3. Spider plot (N=34)**

Table 4. General overview of adverse events (N=36)

**: ≥1 treatment and ≥1 post-baseline tumor staging + measurable target lesion post baseline

Figure 5. Tumor growth kinetics (N=19)*

% changefrombaseline

**: ≥1 treatment and ≥1 post-baseline tumor staging + measurable target lesions post baseline.

0

2

• • Tumour growth kinetics (TGK) obtained as a comparative ratio of the difference of the sum of the largest diameters of target lesions in the pre- and post-baseline setting (Figure 5)2.

• • 73.7% of evaluable patients had post-treatment TGK shrinkage or deceleration (Table 3).

Table 2. Best overall response (iRECIST), N=36

Tumor response (iRECIST)*

Overall n (%)

Complete Response

0 (0)

Partial Response Stable Disease Progression Not Evaluable**

2 (5.6)

11 (30.6)

22 (61.1)

1 (2.8)Overall Response Rate (ITT)

2/36 (5.6)Disease Control Rate (ITT)

13/36 (36.1)Overall Response Rate (evaluable pts)Disease Control Rate (evaluable pts)

4

6

8

12 14 16 18 20 22 24

Time (months)

Table 3. Tumor growth kinetics, N=19#

Tumor dynamics	n (%)
Shrinkage	4 (21.1)
Deceleration	10 (52.6)
Acceleration	5 (26.3)

# ...evaluable set (N=19): ≥1 pre- and post-baseline scan following the same tumors

• • Two confirmed partial responses (5.6%), 36 % disease control rate leading to 26% with long-term (6+ months) disease control in very difficult to treat (PD-X refractory NSCLC) patient population.

  Figure 6. Single case #1

  • • 71-year-old female diagnosed with metastatic NSCLC (NSQ) in Sep 2016.

  • • Received 1st line carboplatin + pemetrexed + pembrolizumab for 18 months  stopped due to PD.

  • • At study entry: ECOG 1, non-evaluable PD-L1 TPS, EGFR/ALK negative, ex-smoker

  • • Started TACTI-002 in Feb 2020 and is still on therapy (Jan 2022) with confirmedongoing partial response (-87%)

  PRE-STUDY (DEC 2019)

  PD on basis of skeletal metastases.

  2/35 (5.7)

  13/35 (37.1)

  No supraclavicular lymphadenopathy seen at this point

  BASELINE (FEB 2020)

  Further PD confirmed with new left supraclavicular lymph node measuring 1.5cm

  POST 3 CYCLES (APR 2020)

  Left supraclavicular node shrunk to 5mm (-67%)

  Figure 7. Single case #2

  • • 67-year-old female diagnosed with metastatic NSCLC (NSQ) in Aug 2019.

  • • Received 1st line cisplatin + pemetrexed + pembrolizumab for 8 months. discontinuing after progression.

  • • At study entry: ECOG 0, PD-L1 80 %, EGFR/ALK negative, non-smoker, several metastatic sites (lung, lymph nodes).

  • • Started TACTI-002 in Apr 2021 and is still on therapy (Jan 2022) with confirmed partial response (-38 %).

  CONCLUSION

  # 11P

  Lymph Node LesionLung LesionPRE-STUDY (Feb 2020)

  BASELINE (APR 2021)

  Safety parameter	n (%)
  Patients with any TEAE	35 (97.2)
  Patients with any SAE	8 (22.2)
  thereof related to efti/pembro	1 (2.8)/1 (2.8)
  Patients with any grade ≥3 TEAE	13 (36.1)
  thereof related to efti/pembro	1 (2.8)/3 (8.3)
  Patients with fatal TEAEs*	3 (8.3)*
  thereof related to efti /pembro	0
  Patients with TEAEs leading to discontinuation of any study treatment	3 (8.3)

  *... metastatic neoplasm; dyspnea, acute respiratory failure (each occurring once)

  • • Pts received a median of 5 (range 2-31) pembrolizumab and 7 (range 2-22) efti administrations.

  • • The most common TEAEs were dyspnea (33.3%), decreased appetite (33.3%), and cough (25%) (Table 5). No treatment-related deaths occurred (Table 4).

  Table 5. Frequent treatment-emergent adverse events occurring ≥15% (N=36)

• • Encouraging early OS data with 6-months landmark analysis showed 73 % survival rate.

• • The combination of an APC activator (efti) plus PD-1 antagonist (pembrolizumab) is well-tolerated and shows signs of antitumor activity in PD-X refractory 2nd line NSCLC patients.

  Adverse event (PT)	Any grade N (%)	Grade 3 N (%)	Grade 4/5 N (%)
  Dyspnoea	12 (33.3)	2 (5.6)	-
  Decreased appetite	12 (33.3)	-	-
  Cough	9 (25.0)	-	-
  Asthenia	8 (22.2)	1 (2.8)	-
  Fatigue	6 (16.7)	1 (2.8)	-
  Weight decreased	6 (16.7)	-	-

• • This combination warrants further clinical investigation in this setting.

CYCLES (JAN 2022)POST 12

ALK…Anaplastic Lymphoma Kinase APC…antigen-presenting cell ECOG…Eastern Cooperative Oncology Group EGFR…Epidermal growth factor receptor iRECIST…Immune Response Evaluation Criteria In Solid Tumors ITT…Intent to treat population

LAG-3...Lymphocyte Activation gene-3 MHC…Major Histocompatibility Complex NSCLC...non-small cell lung cancer PD-L1...Programmed Death ligand-1 PD-X...PD-1 or PD-L1 targeted therapy PFS...progression-free survivalPT...preferred term ORR…objective response rate SAE…serious adverse event TEAE…treatment-emergent adverse event TPS…Tumor Proportion Score TGK…tumor growth kinetics