Crossing over would signify progression. There is another situation whereby an interim analyssi shows significant improvement with one of the arms and then patients are allowed to crossover as the trial is successful.
For Meteor it is far better to not allow crossover, it makes for cleaner data, and thus more straightforward statistical conclusions.
If crossover is allowed that would mean a patient on treatment arm A, with progression could "crossover" to the treatment on arm B.
No crossover allowed means you can't; therefore, with progression you would come off the trial and that data event is then documented as "progression" at that time point.
That would mean coming off trial with progressive disease or intolerance of the treatment arm you were assigned. Patients like that are still followed for OS data, that is what hurt Comet1, and late adverse events are logged.
Agree that nothing matters but the Meteor results; however, I still contend that the company asking for Fast Track status, and it being granted, can only be interpreted in a positive light. For those of us who aren't "traders" it actually matters little as we are here for the whole drug development to market economics game; not timingthe news, and trends and riding the "animal spirits" in the market.
What I find most intriguing, is the penultimate paragraph. What it implies here then is that EXEL asked for the Fast Track status within the last 60 days...hmmmmmm
From FDA website, I found this interesting, you might as well:
Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.
Determining whether a condition is serious is a matter of judgment, but generally is based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more serious one. AIDS, Alzheimer’s, heart failure and cancer are obvious examples of serious conditions. However, diseases such as epilepsy, depression and diabetes are also considered to be serious conditions.
Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy.
Any drug being developed to treat or prevent a condition with no current therapy obviously is directed at an unmet need. If there are available therapies, a fast track drug must show some advantage over available therapy, such as:
•Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
•Avoiding serious side effects of an available therapy
•Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
•Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
•Ability to address emerging or anticipated public health need
A drug that receives Fast Track designation is eligible for some or all of the following:
•More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
•More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
•Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
•Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA
Fast Track designation must be requested by the drug company. The request can be initiated at any time during the drug development process. FDA will review the request and make a decision within sixty days based on whether the drug fills an unmet medical need in a serious condition.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
I agree that an approval based upon 125 patients would be very unlikely. But if very significant results I could imagine an NCCN Compendia listing being entertained. At the very least I would expect a large BioPharma to stand up and take serious notice about the potential for Cabo in numerous indications. The crazy thing is, that very same announcement a year ago would have moved this same stock a number of dollars I would think.
I for one am looking forward to an interesting 2-3 months. Gawd knows that last 6 months have been atrocious.
The thing is...IF they present positive PFS and/or OS for NSCLC with or without Tarceva...that would be an absolutely blockbuster indication ($billions)...far bigger than Comet1. I am curious as to why these statements they made publicly aren't getting any love? Seems very strange to me. It would be like them stating Comet1 ineterim analysis is highly stat sig, and the investing world repsonds with crickets; except this (NSCLC) indication is even bigger. Why the silence in the investing world?
Imagine over the next few months: positive RCC trial, positive with/without Tarceva in NSCLC...huge share price increase would be virtually certain. Buyout almost as certain from Roche. Keep in mind, nowadays if very compelling data and already have FDA approval for thyroid (Exam trial, did all the safety data work already) they would only need the NCCN to agree that it is of value based upon the science in lung ca, and it would be paid for.
From their SEC document....interesting, and intriguing.
Could there be a surprise at ASCO in June?
In November 2014, we announced positive top-line results from a randomized phase 2 trial of cabozantinib and erlotinib alone or in combination as second- or third-line therapy in patients with stage IV EGFR wild-type NSCLC. This trial (Study E1512) is sponsored through our CRADA with NCI-CTEP. Study E1512 was designed and is being conducted by the ECOG-ACRIN Cancer Research Group.
In the E1512 trial, 125 patients were randomized to one of the three arms: erlotinib, cabozantinib, or the combination. During a pre-planned interim ECOG-ACRIN Data Safety Monitoring Committee analysis for futility, it was determined that the trial met its primary endpoint of improving progression-free survival (PFS) with cabozantinib alone and also with the combination of cabozantinib plus erlotinib, as compared to erlotinib alone, and the results were highly statistically significant. Safety data were consistent with those observed in other trials of cabozantinib. At the time of analysis, the median follow-up was 5.9 months and overall survival data were immature. The results of the trial are the subject of ongoing analyses and will be submitted by the investigators for presentation at a future medical conference.