Theralase Technologies Inc. V.TLT

Pivotal Phase 2 Trial for NSCLC ?

[Eoganacht]

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.

[CancerSlayer]

Eoganacht wrote: "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

[enriquesuave]

Roche fails in NSCLC PH3 trial.  They will need Rutherin. https://www.reuters.com/business/healthcare-pharmaceuticals/roches-late-stage-trial-two-lung-cancer-drugs-fails-2022-05-11/  

[ScienceFirst]

Nice post Enrique. That's simply another demonstration that immunotherapies, even in combo, are a waste of time for big pharmas and that the first one that will dare stepping in with our ACT platform could prove to brilliant. In a study, a combination of the new drug tiragolumab and Roche's established Tecentriq drug did not slow disease progression in newly diagnosed cases of advanced

[enriquesuave]

There is no question about it IMO.  Combination immunotherapy has its limits.  The ideal combination is one made of a potent drug which destroys entire tumors and  cancers cells via ICD ( immunogenic cell deaths) combined with either checkpoint inhibitors or immune activators.  IMO  TLD-1433/ Rutherin PDT does exactly and most elegantly what is needed, and when added to

[stocksnbonds458]

Could you imagine how much of a monster TLT would be if their drug is as effective on NSCLC as it is on Bladder cancer? Lung cancer is responsible for 23% of all cancer deaths in the US, 83% of those deaths were diagnosed with NSCLC. What a miracle it would be, so may lives would be saved!

[Tapps21]

I think we have all been imagining, wondering and dreaming for what seems/feels like eternity what this wonder drug can achieve. You are definitely not alone as we all wait with bated breath.