Do patients with BRAF-mutated non-small cell lung cancer benefit from treatment with Cotellic (cobimetinib) and Zelboraf (vemurafenib)?  The first expansion cohort in ProTarget

The cohort including patients (pts.) with BRAF V600-mutated non-small cell lung cancer (NSCLC) for treatment with Cotellic (cobimetinib) and Zelboraf (vemurafenib) has completed the first stage of accrual. The cohort has been evaluated and treatment benefit is seen for ≥1 pt. Therefore, the investigator group has decided to expand the cohort to enroll an additional 16 pts. (figure 1).

“This is an important first step for the trial and the patients. I am confident that we will be able to complete the next stage with our international collaborators to provide additional evidence.”

Professor Ulrik Lassen, Study Principal Investigator, ProTarget.

The combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is approved by EMA for treatment of BRAF V600-mutated metastatic melanoma. However, in ProTarget this combination therapy is tested outside the approved label in pts. with BRAF-V600 mutated advanced cancer and patients are included in cohorts defined by their genomic match and tumor type. The pts. included in ProTarget must have exhausted all standard treatment options. The expansion of the cobimetinib+vemurafenib/BRAFmut/NSCLC-cohort may provide us with data indicating treatment benefit in this patient group.

When the cohort completes second stage of accrual (24 pts), patient characteristics, response and toxicity data will be summarized and evaluated. If at least 5 pts. demonstrate benefit of treatment, further investigations may be initiated. One option may be to enter stage 3 in collaboration with other DRUP-like trials in Europe by pooling data and continue patient inclusion across the trials within the PrimeRose consortium, a Horizon 2022 project funded by the European Union.

Figure 1. Patients are enrolled in cohorts defined by the drug, tumor genomic match and tumor type. Upon enrollment of 8 pts. (stage 1), the cohort is evaluated. If at least one pt. has benefit of treatment, the cohort is expanded with an additional 16 pts. to reach 24 pts (stage 2). A positive signal of drug activity will be concluded if at least 5 pts. among the 24 pts. demonstrate treatment response or stable disease and may lead to further investigations.