FDA Gives Positive Feedback on Phase 3 Eftilagimod Alfa NSCLC Trial Design

The FDA has given positive feedback on the design of the phase 3 TACTI-004 trial intended to assess eftilagimod alfa (efti) plus pembrolizumab (Keytruda) and chemotherapy for patients with metastatic non–small cell lung cancer (NSCLC) of any PD-L1 expression status, according to a press release from the developer, Immutep Limited.¹

The feedback from a Type C meeting indicates the end of preparatory regulatory meetings on the registrational trial’s design. Investigators of TACTI-004 plan to enroll approximately 750 patients regardless of PD-L1 expression in their assessment of the efti-based combination.

In the double-blind, international TACTI-004 trial, patients will be randomly assigned 1:1 to receive efti or matched placebo in combination with pembrolizumab and standard chemotherapy as first-line therapy for squamous or nonsquamous metastatic NSCLC. The trial’s dual primary end points will be progression-free survival (PFS) and overall survival (OS). Investigators will evaluate these end points based on a prespecified futility boundary and a pre-planned interim analysis.

“We are pleased with the FDA’s feedback, as this allows us to successfully conclude our regulatory preparation for the TACTI-004 registrational trial,” Christian Mueller, senior vice president of Regulatory and Strategy at Immutep, said in the press release.¹ “This represents a key milestone in our late-stage development process for efti centered on potentially driving a new standard of care globally in the treatment of [NSCLC]. We hope to achieve this through efti in combination with [pembrolizumab], which has led to strong efficacy data with a favorable safety profile in [patients with frontline] NSCLC regardless of PD-L1 expression.”

The Paul-Ehrlich-Institut, a German regulatory authority associated with the Committee for Medicinal Products for Human Use, previously offered feedback on the design of the TACTI-004 trial in December 2023.² At the time, the agency expressed its support of developers assessing efti in combination with anti–PD-1 therapy for patients with first-line NSCLC as part of a registrational trial.

Additionally, developers received positive feedback from the Spanish Agency for Medicines and Health Products (AEMPS) Competent Authority on the TACTI-004 trial’s design in April 2024.³

“We continue to be pleased with our discussions with regulatory bodies around the world regarding our upcoming pivotal TACTI-004 trial and are thankful for the positive feedback and constructive guidance received by AEMPS,” Mueller said in a press release at the time of the Spanish regulatory authority’s feedback.³

Supporting data for the TACTI-004 trial’s assessment of efti in front-line NSCLC came from the phase 2 TACTI-002 trial (NCT03625323) and the INSIGHT-003 trial.

According to data from part C of TACTI-002 presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, efti plus pembrolizumab elicited an objective response rate (ORR) of 30% across the intent-to-treat population (n = 37), which included complete responses in 14%.⁴ Data showed responses with the combination therapy across all PD-L1 subgroups. Additionally, the median PFS was 2.1 months, and the median OS was 8.7 months.

Previous data from INSIGHT-003, which investigators presented at the 2023 European Society for Medical Oncology (ESMO), showed that the median OS was not reached and the median PFS was 10.1 months in patients who received efti plus pembrolizumab and doublet chemotherapy.⁵ Study treatment also conferred an ORR of 71.4% and a disease control rate of 90.5%. The combination therapy also appeared to be safe in this population; according to the investigators, adding efti did not increase the toxicity associated with the standard chemoimmunotherapy regimen.

References

1. Immutep announces successful meeting with FDA on phase III design in non-small cell lung cancer. News release. Immutep Limited. July 22, 2024. Accessed July 23, 2024. https://tinyurl.com/mw43epzc
2. Immutep receives constructive regulatory feedback on TACTI-004 registrational trial in metastatic non-small cell lung cancer. News release. Immutep Limited. December 21, 2023. Accessed July 23, 2024. https://tinyurl.com/yc8dy22s
3. Immutep receives positive feedback from the Spanish Medicines Agency for upcoming TACTI-004 registrational trial in metastatic non-small cell lung cancer. News release. Immutep Limited. April 17, 2024. Accessed July 23, 2024. https://tinyurl.com/4khwazjd
4. 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
5. Immutep reports promising clinical data from INSIGHT-003 trial at ESMO Congress 2023. News release. Immutep Limited. October 24, 2023. Accessed July 23, 2024.