Pivotal Phase 2 Trial for NSCLC ?I think one of the reasons Theralase may have chosen NSCLC as their next cancer indication is that, like NMIBC, it's possible to get approval from the FDA based on a pivotal phase 2 trial. Treatment for NSCLC is complicated by the fact that there are more than a dozen gene mutations linked to the disease. When someone is diagnosed with NSCLC a biopsy of their tumour may be taken to determine what gene mutation is responsible. It may then be possible to use a targeted treatment for that mutation.
For example up to 10-35 percent of NSCLC tumours contain the EGFR mutation. Targeted treatments (EGFR inhibitors) for this mutation include:
- afatinib (Gilotrif)
- dacomitinib (Vizimpro)
- erlotinib (Tarceva)
- gefitinib (Iressa)
- Necitumumab (Portrazza)
- osimertinib (Tagrisso)
Gene Mutations in Non-Small-Cell Lung Cancer 
There are "approved" treatments for these gene mutations:
EGFR ALK ROS1 BRAF NTRK
There are "off-label" treatments for these gene mutations:
HER2 MET RET
There are clinical trials for these gene mutations:
KRAS PIK3CA AKT1 PTEN And there is now a treatment for
KRAS G12C, a driver mutation found in about 13% of Patients with Non-Squamous Non-Small Cell Lung Cancer that received FDA accelerated approval.
Below is a link to the NDA Multi-disciplinary Review and Evaluation document for the phase 2 pivotal trial of Amgen's sotorasib for patients with locally advanced or metastatic
NSCLC with KRAS G12C mutation which led to the approval.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214665Orig1s000MultidisciplineR.pdf "The submitted evidence meets the statutory evidentiary standard for accelerated approval. The effect of sotorasib on durable ORR observed in the primary efficacy population from Study 20170543 demonstrates a meaningful advantage over that achievable with FDA-approved available therapies for this refractory population. ORR of large magnitude and long duration is an endpoint reasonably likely to predict clinical benefit in NSCLC and has supported the accelerated approvals of multiple other targeted therapies for patients with NSCLC harboring oncogenic driver mutations (Blumenthal 2015). This is the first approval of a targeted therapy for patients with KRAS G12C mutated NSCLC; the ORR and DOR results are supported by a favorable safety profile and ease of administration over currently available therapies. " ("Overall response rate, or ORR, is the proportion of patients in a trial whose tumor is destroyed or significantly reduced by a drug. ORR is generally defined as the sum of complete responses (CRs) – patients with no detectable evidence of a tumor over a specified time period – and partial responses (PRs) – patients with a decrease in tumor size over a specified time period. Improved ORR offers tangible proof that the drug is working. ")
https://www.astrazeneca-us.com/media/astrazeneca-us-blog/2018/clinical-trial-endpoints-in-cancer-research-four-terms-you-should-know-09242018.html#! If a NSCLC treatment can achieve a durable ORR and demonstrate a meaningful advantage over that achievable with FDA-approved available therapies for a refractory population then they are a candidate for accelerated approval in a pivotal phase 2 trial. And since Rutherrin should work on any NSCLC tumour cells, and is not restricted to any particular mutation, as transferrin receptors are over-expressed in all NSCLC cells, the refractory population for a Rutherrin trial could be large.