WCLC 2022 | JAVELIN Lung100, PRIMUS, NintNivo, IMpower010: investigating IO in NSCLC

I would like to a little bit, the journey of immunotherapy across lung cancer. So one of the trials which I have had the privilege to present here is the JAVELIN 100 trial investigating a monotherapy with an Anti-PD-L1 antibody, avelumab against platinum based chemotherapy. A very large trial more than 1,200 patients were randomized between avelumab. We had two arms, one high dose arm, one conventional dose arm platinum-based chemotherapy, compared to chemotherapy alone. The primary endpoint was the progression-free survival and the overall-survival in the group of patients with high PD-L1 expression. There was a signal of efficacy favoring the avelumab monotherapy. Unfortunately, this trial didn’t reach statistical significance and currently we are evaluating these outcomes. Currently, some reason in the changing landscape of immunotherapy in patients with non-small cell lung cancer we have an uptake of immunotherapy, also at later lines of therapy. This might have contributed to the outcomes.

Well, the next point is to look at something which is behind the first line. This is the maintenance, and we performed a small trial in Germany, the PRIMUS trial, investigating a maintenance with pembrolizumab compared to placebo in patients with squamous cell carcinoma who had received a first-line chemotherapy. Unfortunately we had to close the trial due to slow accrual, but there was a clear signal in the efficacy favoring this maintenance treatment with pembrolizumab.

And there’s also another important question. This is the question of re-exposition of checkpoint inhibitors who are progressing after the maintenance therapy with a checkpoint inhibitor. And there, we had a very interesting paper here in Vienna, summarizing all the second cause the re-exposition data for patients in the KEYNOTE trials. These were roughly 60 patients and we were looking on the activity of this re-exposition with pembrolizumab.

And we had two cohorts. One was the cohort of patients who had received a monotherapy with pembrolizumab for two years, then the follow-up and then the re-exposition at time of progression. And we also had a small group of patients who had received the combination of pembrolizumab with chemotherapy, followed by the maintenance of two years to follow-up. And then the Pembrolizumab as a second cause. What we do see is that there a signal of clinical efficacy, we have a response rate of roughly 20%, but we do see a significant stabilization of the disease. And we do see so far a six month overall-survival rate, which is in the range of 85%. And I think this is a great signal for a re-exposition of pembrolizumab.

Well, moving along with the journey, the next step is the resistance after immunotherapy and this is a difficult area. We are currently conducting several tribes. We have done a small trial in Germany evaluating the combination of nintedanib which is an antiangiogenic oral agent with nivolumab as a checkpoint inhibitor. And interestingly, very similar to the data from Karen Reckamp from the MAPs trial, we have seen not so much activity in terms of response of progression-free survival, but we have seen a median overall-survival of more than 12 months and we still have five patients on treatment. So there is something ongoing for this addition of nintedanib which is an antiangiogenic to checkpoint locate. And this is something to follow up.

Lastly, I would like to talk about early stages of lung cancer and there we had two major data sets presented here in Vienna. Number one was an update on the IMpower010, the adjuvant trial investigating atezolizumab in resected patients following adjuvant chemotherapy. Then Enriqueta Filip presented the overall-survival data and interim analysis. And we have seen in the trial population, the PD-L1 positive patients, a significant improvement in overall-survival favoring the adjuvant therapy with atezolizumab. And furthermore, when we look on the indication, which is labored in Europe, these are the patients with high PD-L1 expression. There was really a remarkable benefit in overall-survival corresponding to a hazard ratio of 0.43.

And lastly, a study from Spain was presented. This was an update, the NADIM II trial, investigating a neoadjuvant chemo immunotherapy compared to neoadjuvant chemotherapy in patients with stage three non-small cell lung cancer. And Dr Provencio reported the progression-free survival and the overall-survival data for this trial and similar to the primary outcomes in pathological response and event-free survival. There was also a significant prolongation of progression-free survival and overall-survival in favor of those patients who had received the neoadjuvant chemoimmunotherapy. So we have a bunch of new data and I think immunotherapy really has conquered lung cancer. Now we are trying to explore whom to treat, when to treat and how long to treat. Thank you.