TACTI-002 Data Show Antitumor Activity With Second-Line Eftilagimod Alpha and PD-1 Inhibition in HNSCC


Bernard Doger de Spéville, MD, PhD, discusses the investigation of eftilagimod alpha plus pembrolizumab in the TACTI-002 trial, including prior evidence supporting this approach, the trial’s design and primary objective, and the combination’s efficacy and safety in both the head and neck squamous cell carcinoma and non–small cell lung cancer cohorts.

Bernard Doger de Spéville, MD, PhD

Bernard Doger de Spéville, MD, PhD

The response rates and tolerability seen with the first-in-class MHC class II agonist eftilagimod alpha (efti; IMP321) in combination with pembrolizumab (Keytruda) in patients with head and neck squamous cell carcinoma (HNSCC) illustrate the regimen’s success in broadening and strengthening immune responses regardless of PD-L1 status, according to Bernard Doger de Spéville, MD, PhD.

In part C of the phase 2 TACTI-002 trial (NCT03625323), patients with HNSCC unselected for PD-L1 expression received eftilagimod alpha plus pembrolizumab in the second line. Data presented at the 2023 ASCO Annual Meeting showed that the regimen produced an objective response rate (ORR) of 29.7% (95% CI, 15.9%-47.0%) by iRECIST criteria in the intent-to-treat population (n = 37), which included a 13.5% complete response rate and a 16.2% partial response rate. Responses occurred across PD-L1 subgroups. At a median follow-up of 38.8 months, the median duration of response was not reached.1

Data from cohorts A and B of patients with first-line, PD-1/PD-L1–naïve non–small cell lung cancer (NSCLC) and second-line, PD-1/PD-L1–refractory NSCLC, respectively, were previously reported. The regimen provided a clinically meaningful initial overall survival benefit in both populations.2,3

“We have seen an increase in efficacy when combining [eftilagimod alpha] with other drugs, without increasing the risk or the [frequency] of adverse effects. It’s a good, well-tolerated drug with great efficacy outcomes,” said de Speville, who is a medical oncologist and member of the Early Phase Clinical Trials Unit at START Madrid-Fundacion Jimenez Diaz, in Madrid, Spain.

In an interview with OncLive®, de Speville discussed the investigation of eftilagimod alpha plus pembrolizumab in the TACTI-002 trial, including prior evidence supporting this approach, the trial’s design and primary objective, and the combination’s efficacy and safety in both the HNSCC and NSCLC cohorts.

OncLive: Please provide some background on the phase 2 TACTI-002 trial, including any previous research that supported the investigation of eftilagimod alpha plus pembrolizumab in patients with HNSCC and NSCLC.

de Speville: This is an early-phase, clinical trial with 3 arms. We are publishing data from arm C, which is [composed of] patients [with] HNSCC [in the] second line.

We already had previous data [on the treatment of] these patients with chemotherapy, mainly platinum-based chemotherapy. After the [phase 3] KEYNOTE-048 trial [NCT02358031], we saw that these patients had very good outcomes when combining chemotherapy with pembrolizumab. [This includes] patients with a PD-1 combined positive score [CPS] above 20. [Patients treated] with pembrolizumab monotherapy [also] had very good outcomes. The rationale for this trial is to combine an anti–PD-1 therapy such as pembrolizumab with eftilagimod alpha to enhance T-cell [activation] in this [population. The trial included] chronic patients with metastatic HNSCC who have already received first-line platinum-based chemotherapy.

What is the mechanism of action of eftilagimod alpha? What is the advantage of administering it in combination with pembrolizumab in these tumor types?

Eftilagimod alpha is a soluble LAG-3 protein. This protein binds to MHC class II and this triggers the [CD4/CD8] T-cell [activation. By] combining this drug with pembrolizumab, an anti–PD-1 antibody, we can increase the number of CD8-positive T cells in the tumor microenvironment. The reason for combining these 2 drugs is to enhance the action of these 2 drugs [compared with their activity as] monotherapies.

What efficacy and safety findings from this study were presented at the 2023 Annual ASCO Meeting?

We reported data on the primary end point, which is ORR. In this trial, we achieved a [29.7%] ORR in all patients. If we compare [this result] with [what has been observed in] other trials of pembrolizumab alone, [such as KEYNOTE-048, the ORR has] almost doubled. This is very encouraging for this [population].

We also reported safety data [showing that] this combination was safe. Eftilagimod alpha is a subcutaneous drug. This drug is administered every 2 weeks for the first 9 cycles [plus] pembrolizumab [given] every 3 weeks. The cycles are 21 days [each]. The main toxicities that we saw were site injection reactions. For every [injection], we switch the side of administration [to potentially mitigate this]. It’s mainly a mild site injection reaction and is not usually painful. Sometimes [patients may experience] grade 1/2 pruritis, but [the drug is overall] very well tolerated.

How did these outcomes in patients with HNSCC compare with responses observed in the NSCLC cohorts?

We had 2 different cohorts for NSCLC [in this trial]. One of them is a first-line population [being treated] with the combination, and the other one is [patients in the] second line [who progressed after standard-of-care treatment with a PD-1/PD-L1 monotherapy or chemotherapy plus anti–PD-1/PD-L1 therapy]. These data were reported at the 2022 ESMO Congress. 

In terms of efficacy, [results in these patients were] similar to what we’re seeing in the HNSCC [cohort]. In terms of tolerability, we haven’t seen any increases of adverse effects [AEs] or treatment-emergent AEs. We have also seen good outcomes [in both NSCLC] populations despite PD-L1 status, as we see in the HNSCC cohort.

Are there any other planned or ongoing investigations of eftilagimod alpha and pembrolizumab in solid tumors?

We have another [phase 2] trial ongoing for [patients with] HNSCC [in the] first line, regardless of PD-L1 status [called TACTI-003 (NCT04811027)]. There are also trials [of eftilagimod alpha and pembrolizumab] ongoing [in] other solid tumors, such as breast cancer. We hope that the efficacy will also be very good [in these tumor types]. In terms of tolerability, we believe that [the regimen] will be safe [in these cancers].

Disclosures: Dr Doger de Spéville had no relationships to disclose.


  1. de Spéville BD, Felip E, Forster M, et al. 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. J Clin Oncol. 2023;41(suppl 16):6029. doi:10.1200/JCO.2023.41.16_suppl.6029
  2. Immutep’s efti in combination with pembrolizumab achieves excellent initial overall survival benefit in 1st line non-small cell lung cancer. News release. Immutep. May 17, 2023. Accessed August 23, 2023. https://www.immutep.com/detail/2023
  3. Immutep’s efti in combination with MSD’s pembrolizumab shows encouraging antitumor activity in difficult to treat 2nd line metastatic lung cancer patients. News release. Immutep Limited; March 30, 2022. Accessed August 23, 2023. https://www.immutep.com/files/content/investor/press-release/2022/

Editor’s Note: This interview was conducted prior to the conclusion of the 2023 ASCO Annual Meeting.

Related Videos
Julien Hadoux, MD, PhD, medical oncologist, attending physician, Gustave Roussy, Villejuif, France
David Sher, MD
Joachim G. J. V. Aerts, MD, PhD
Nathaniel Myall, MD
Martin Cannon, PhD, professor, Department of Microbiology, University of Arkansas for Medical Sciences College of Medicine
Pedro Barata, MD, MSc
In this fourth episode of OncChats: Examining LIFU–Aided Liquid Biopsy in Glioblastoma, Manmeet Singh Ahluwalia, MD, and Michael W. McDermott, MD, discuss the key objectives of the phase 3 LIMITLESS study (NCT05317858) examining low-intensity focused ultrasound with immunotherapy and chemotherapy in patients with lung cancer and brain metastases.
Nabil F. Saba, MD, FACP
Jun Ma, MD
Bernard Doger de Spéville, MD, PhD