JUNO - Confusion on stage of JCAR017

On Nov. 1, 2017, JUNO updated phase 1/2 trial data of JCAR017 (CAR-T therapy for r/r B cell non-Hodgkin lymphoma - cancer). The result is quite impressive:

* Dose level 2 (DL2 = 100 million cells), the dose in the pivotal cohort for the TRANSCEND study, showed a 3 month overall response rate (ORR) of 80% (12/15) and a 3 month complete response (CR) rate of 73% (11/15) in the core group. Data support a dose response relationship. Dose level 1 (DL1 = 50 million cells) showed 3 month ORR of 52% (11/21) and a 3 month CR rate of 33% (7/21).
* Across both doses in the core group, the best overall response was 84% (41/49) and the best overall CR rate was 61% (30/49).
* There was no increase in cytokine release syndrome (CRS) and neurotoxicity (NT) rates associated with the higher dose or between the full and core groups. Across doses in the full group, 1% (1/69) experienced severe CRS and 14% (10/69) experienced severe NT. 30% (21/69) had any grade CRS and 20% (14/69) had any grade NT. 64% (44/69) had no CRS or NT.
* The most common treatment-emergent adverse events other than CRS and NT that occurred at =25% in the full group included neutropenia (41%), fatigue (30%), thrombocytopenia (30%), and anemia (26%).

More advances in CD19- And BCMA-Targeted CAR-T therapy will be presented on Dec. 11, 2017 at ASH (see the link below).

Here comes my naive question: what is the current stage for JCAR017, phase 1, phase 2 or phase 3? According to the link below, the current stage is a combined phase 1/2 trial, which is also a pivotal trial. Does that mean JUNO can skip the phase 3 trial and apply for approval from FDA if everything goes smooth?




Juno’s JCAR017 is in Phase 1, according to the NIH:

Scroll down and note the following:

Estimated Enrollment:	           274
Study Start Date:	           December 2015
Estimated Study Completion Date:   April 2020
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)

The NIH site provides fantastic up-to-date info very easily. I went to the NIH website at
https://clinicaltrials.gov and entered:
B cell lymphoma
United States
And clicked” Find a study to participate in.”

BTW, there’s no skipping any phases.



Hi Ray,

Thank you very much for your answer. Below is the explanation for pivotal trial from Wiki:

“A pivotal trial is a clinical trial or study intended to provide evidence for a drug marketing approval, e.g. by the United States Food and Drug Administration. Phase III trials are assumed to be pivotal so the phrase is often used for the rare pivotal phase II trials.”

My question is why phase 1 trial can be a pivotal trial? Since pivotal trial is a clinical trial or study intended to provide evidence for a drug marketing approval, is it necessary to do another phase 3 pivotal trial after a phase 1 or 2 pivotal trial?

BTW, as I remember, there is no phase 3 trial for KITE’s CAR-T therapy, at least I could not find the related information. Please feel free to correct me if I am wrong.