695 Efficacy and safety of trastuzumab deruxtecan (T-DXd) with durvalumab in patients with non-small cell lung cancer (HER2 altered NSCLC) who progressed on anti-PD1/PD-L1 therapy (HUDSON)

Background

The HUDSON platform study (NCT03334617) explores investigational therapies in patients (pts) with NSCLC who progressed on immune checkpoint inhibitors (ICIs) to overcome immune resistance in the post-ICI setting. HUDSON allocated treatment based on biomarker selection or on time (<24 vs. ≥ 24 weeks) before progression on prior ICI. Here, we report on the results of Durvalumab (anti-PD-L1) + T-DXd (anti-HER2 antibody drug conjugate) treatment (module 6) in pts with HER2 overexpressing or HER2 mutant tumours.

Methods

Pts had documented advanced/metastatic NSCLC with centrally confirmed HER2 overexpression (HER2e) or activating mutations (HER2m), received platinum-based therapy and progressed on prior ICI. Pts received durvalumab 1120 mg iv and T-DXd 5.4 mg/kg iv every 3 weeks until disease progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria; secondary endpoints included progression-free survival (PFS), overall survival (OS) and frequency of adverse events (AEs).

Results

A total of 43 pts (HER2e n=23, HER2m n=20) started therapy between 23/6/2020 and 16/9/2021. Differences in main demographic and disease characteristics at study entry were observed between HER2e and HER2m pts (sex, smoking status, extent of disease, primary resistance to prior ICI; extended report of the characteristics at the conference). Confirmed ORR was 26.1% (80% CI, 14.3–41.3) in HER2e pts and 35% (80% CI, 20.7–51.8) in HER2m pts. Median PFS was 2.8 mo (80% CI, 2.2–5.5) in HER2e pts and 5.7 mo (80% CI, 5.5–6.5) in HER2m pts. Median OS was 9.5 mo (80% CI, 6.6–12.4) in the HER2e group and 10.6 mo (80% CI, 8.9-NC) in the HER2m group. Median duration of follow-up in censored subjects was 16.5 mo (range, 7.3–24.2) in the HER2e pts and 17.1 mo (range, 4.4–27.6) in HER2m pts. Grade (G) ≥3 treatment emergent AEs (TEAEs) occurred in 55% of all pts (61% of HER2e pts, 50% of HER2m pts); the most common G ≥3 AEs were pneumonitis (none were fatal), pulmonary embolism and anemia. All grade and G≥3 treatment-related pneumonitis occurred in 9.3% (8.7% of HER2e pts, 10% of HER2m pts) and in 7% (8.7% of HER2e pts, 5% of HER2m pts) of all pts, respectively.

Conclusions

Durvalumab+T-DXd combination was tolerated and showed antitumor activity in HER2 altered NSCLC in the post-ICI setting, with a trend toward higher response in HER2m pts. The small sample size limits the overall conclusions of the study.