Lion the first beneficiary of NCI’s trial resumption

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The suspension of 13 cell therapy studies at the US National Cancer Institute in April cast uncertainty on their corporate partners, but less than three months later, and with little fanfare, five have resumed patient enrolment.

This is good news for Lion Biotechnologies, as the five include all three of the tumour-infiltrating lymphocyte studies that are subject to a co-operative R&D agreement it has with the NCI. Four trials for which Kite Pharma has a separate CRADA remain suspended, but should reopen within three months, an NCI spokesperson told EP Vantage.

This means that the suspensions look to have been less serious than had been suspected at the time. In April the NIH said the move was due to follow-up from an earlier finding of serious problems with sterile manufacturing processes, and concerned an NCI cell therapy lab as well as a facility at the National Institute of Mental Health.

Of course, because CRADAs are arm’s-length arrangements that do not involve a formal licence with a corporate entity, Kite and Lion were able to shrug the suspensions off. Nevertheless, Kite stock was hit amid confusion over disclosure of the halts as well as underwhelming data presented at the AACR meeting (AACR – Mage-A3 double-whammy hits Kite, April 17, 2016).

Lion said the suspensions did not affect its own manufacturing capabilities for tumour-infiltrating lymphocyte (TIL) therapy, as these relied on agreements with Lonza and WuXi AppTec. However, this only told half the story since the suspension concerned the lab of Dr Steven Rosenberg and included the TIL project Lion had accessed under its CRADA.

This now becomes academic, as all three of Dr Rosenberg’s TIL trials reopened for patient enrolment on June 17, said Shannon Hatch, an NCI spokesperson. “We expect the remaining eight trials to reopen for enrolment within three months,” she added.

NCI cell therapy studies suspended in April 2016, now enrolling again
Detail Company affiliation Principal investigator Trial ID
TILs + IL-2 alone or after Keytruda in 170 melanoma pts CRADA with Lion Biotechnologies Dr Steven Rosenberg NCT02621021
Use of TILs in 85 NSCLC pts CRADA with Lion Biotechnologies Dr James Yang NCT02133196
Use of TILs in 64 metastatic melanoma pts CRADA with Lion Biotechnologies Dr Steven Rosenberg NCT01993719
Use of TILs in 290 pts with various solid tumours None Dr Steven Rosenberg NCT01174121
Use of TILs in 57 pts with metastatic ocular or uveal melanoma None Dr Udai Kammula NCT01814046

Lion investors might see this as another line drawn under various simmering problems. The company recently raised $100m in a private placement, and replaced its previous chief executive, Elma Hawkins, with Maria Fardis.

Meanwhile, Kite’s focus remains on filing its lead CAR-T asset, KTE-C19, with the US FDA. Irrespective of the ongoing suspension of the NCI’s Mage-A3 engineered TCR project, Kite’s own studies of this asset are to begin under an IND to be filed later this year.

The other two NCI projects to which Kite has access under a CRADA – a CAR against EGFRvIII and an engineered TCR targeting NY-ESO-1 – also remain suspended for now. Kite has had problems with these, and recently downgraded them both to preclinical status, citing the need for “additional engineering”.

If the NCI’s studies do resume within three months this will not solve such issues, but it should at least remove some of the negative sentiment.

NCI cell therapy studies still suspended as at 4 July 2016
Detail Company affiliation Principal investigator Trial ID
Engineered TCRs vs Mage-A3 in 16 HLA-DP0401-positive pts with various cancers CRADA with Kite Pharma Dr Steven Rosenberg NCT02111850
Engineered TCRs vs Mage-A3 in 3 HLA-A01-positive pts with various cancers CRADA with Kite Pharma Dr Steven Rosenberg NCT02153905
Engineered TCRs vs NY-ESO-1 in 7pts with various solid tumours CRADA with Kite Pharma Dr Steven Rosenberg NCT01967823
CAR-T vs EGFRvIII in 18 malignant glioma pts CRADA with Kite Pharma Dr Steven Rosenberg NCT01454596
CAR-T vs mesothelin in 15 pts with various cancers None Dr Steven Rosenberg NCT01583686
Engineered TCRs vs human thyroglobulin in 68 thyroid cancer pts None Dr James Yang NCT02390739
Use of TILs in 29 pts with HPV-associated cancers None Dr Steven Rosenberg NCT01585428*
TILs cultured with pharmacologic inhibitor of AktKT in metastatic melanoma None Dr Steven Rosenberg NCT02489266**
Note: *marked as active, not rectuiring; **study withdrawn prior to enrolment.
Selected NCI cell therapy studies still suspended for unrelated reasons
Detail Company affiliation Principal investigator Trial ID
CAR-T vs BCMA in 14 multiple myeloma pts None* Dr James Kochenderfer NCT02215967
Donor-derived anti-CD19 allo CAR-T in 42 pts with B-cell malignancies None Dr James Kochenderfer NCT01087294
Note: *Dr Kochenderfer is primary investigator in a separate anti-BCMA CAR-T study of Bluebird Bio's bb2121.

The tables in this story were updated on July 6. To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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