All In One Place: A New Immuno-Oncology Trial Resource

Xconomy National — 

More than 100 years ago, New York bone surgeon William Coley began to suspect that bacterial infections might be improving the outlook for patients also suffering from cancer. The infections were turbo-charging the immune system.

Coley (pictured) would be gratified to see that in 2016 a growing array of immune-boosting cancer treatments are helping some patients in dire straits, including former U.S. President Jimmy Carter, who fought off a life-threatening skin cancer with the help of a new immunotherapy drug. That’s only one patient and one response; hundreds of other people have been through clinical studies. The pool of data reflecting their experiences and their outcomes is expanding, seemingly day by day. But those data are impossible to find all in one place.

As reporters, we find that frustrating. Perhaps you do, too. So we’ve begun this project: a cancer immunotherapy resource that will grow as the data pool grows. We’re aggregating all the trials we can find that have patient outcomes: whether a treatment made people better, and for how long.

We’re doing this in two steps. First, we’re rolling out data for treatments that use live T cells, modified outside the patient’s body to hunt and kill tumor cells more efficiently, then infused back into the patient. Most of these treatments are a patient’s own cells and are known as CAR-T (chimeric antigen receptor T cell) therapies. They have been successful in a small set of blood-borne cancers, but many of the initial stunning results are blunted by the cancer clawing its way back. “Despite high rates of … remission, relapse is a significant [cause] of treatment failure,” wrote Rebecca Gardner of Seattle Children’s Research Institute and her colleagues this year in describing the results of one of their CAR-T studies. Nearly all the 36 kids treated went into remission at first, but the rate of remission after a year was down to 53 percent.

We acknowledge that what we present here only scratches the surface of each trial. To delve into the complexity—the severity of the side effects, for example, or the need to supplement the T cell therapy with bone marrow transplants or chemotherapy—follow the links to the description or papers that contain the results.

We also acknowledge that this table should not be used to compare trial to trial. Instead, use it as a quick overview to see, for example, that CAR-T therapies have had incredible early success treating kids with acute lymphocytic leukemia (ALL), a fast-growing blood cancer that often resists traditional treatments. Adults with ALL have fared well, too, but not as well as kids. Big trials that could lead to regulatory approvals are underway but have yet to divulge data.

Non-Hodgkin lymphoma (NHL), a wide range of lymph-related cancers, is another big CAR-T target because NHL tumors share a protein, called CD19, with ALL and other leukemias that the modified killer T cells can be engineered to sniff out. Kite Pharma (NASDAQ: KITE) of Santa Monica, CA, could have the first approved CAR-T if a big NHL trial holds true to the promise of interim data that Kite released in September.

The first returns are trickling in from a smattering of engineered T cell trials in other blood-borne cancers, such as multiple myeloma, and solid-tumor cancers (lung, breast, etc.). We’ll compile those here, too.

Part two of this project will be a separate table of a different kind of cancer immunotherapy, made from monoclonal antibodies. They’re known as checkpoint inhibitors because they disarm cancer’s ability to evade, or check, the immune system’s detection. Four checkpoint inhibitors have been approved by regulators to date, all for solid-tumor cancers. We hope this becomes a valuable resource for you. Please tell us how to make it more useful, send corrections, and point out trials we have missed. (We know they’re out there.) We’ll add them as quickly as we can.

Table last updated 3/8/17

CAR-T and Other Cell Therapy Clinical Trials

Latest ResultsMain FindingsTrial ID
or Name
axicabtagene ciloleucel (KTE-C19)Kite Pharma2NHL17-Feb24/62 CR (3 mo)
36/101 CR (6 mo)
DLBCL pts lower response rates than TL/PMBCL
Safety (101 pts): 3 deaths, 13% CRS, 28% NE (≥gr3)
axicabtagene ciloleucel (KTE-C19)Kite Pharma1NHL15-Oct3/7 CR (12 mo)ZUMA-1
axicabtagene ciloleucel (KTE-C19)National Cancer Institute1NHL16-Jun11/22 CR, 1 relapseNCT00924326
axicabtagene ciloleucel (KTE-C19)Kite Pharma1/2adult ALL16-DecZUMA-3/4 combined: 9/11 CR
5/13 gr3 or higher CRS
5/13 gr3 or higher neurotox
axicabtagene ciloleucel (KTE-C19)Kite Pharma1/2pediatric ALL16-DecZUMA-3/4 combined: 9/11 CR
5/13 gr3 or higher CRS
5/13 gr3 or higher neurotox
JCAR014*Juno (Fred Hutchinson)1/2CLL, ALL, NHL16-Jun31/33 CR in ALL
19/41 CR in NHL
15/17 CR in CLL
JCAR015**Juno (Memorial Sloan Kettering)1adult ALL16-Jun41/51 initial CR
73% OS (6 mo)
JCAR015**Juno (Memorial Sloan Kettering)1NHL15-Jun5/8 initial CRNCT01840566
JCAR015**Juno2adult ALL17-MarTrial and all JCAR015 development ended after 5 deaths.ROCKET
JTCR016Juno (Fred Hutchinson)1/2AML16-DecPost-BMT treatment 12/12 CR
median follow-up 2+ yrs
JTCR016Juno (Fred Hutchinson)1NSCLC, mesothelioma16-Apr3 treated, 1 PR, 1 €"stable"NCT02408016
JCAR017Juno1NHL16-Dec12/20 CR
gr3-4 neurotox in 3/22 pts
no "severe" CRS
JCAR017Juno (Seattle Children’s)1/2pediatric ALL16-Nov40/43 initial CR (21 days)
51% EFS and 69.5% OS (12 mo)
53% DFS and 74% OS (12 mo)
JCAR018Juno (National Cancer Institute)1pediatric ALL16_AprMedium dose: 3/3 CR (3-6 mo)
Low dose: 1/6 CR w/relapse (3 mo)
CTL019Novartis (U. Penn)1pediatric ALL15-Dec55/59 CR (1 mo)
18/38 CR (12 mo)
CTL019Novartis (U. Penn)2NHL15-Dec7/26 CR (3 mo)
13/26 CR (6 mo)
CTL019U. PennN/Aadult ALL15-Dec15/27 CR
(better rate in group receiving higher dose over 3 days)
CTL019Novartis (U. Penn)1multiple myeloma15-Sep1/10 CR (12 mo)
6/10 PFS (1-8 mo)
CTL019Novartis (U. Penn)2pediatric ALL16-Dec41/50 CR (3 mo)
25/50 relapse free (6 mo)
48% serious CRS; no deaths
CTL019Novartis2adult DLBCLN/ADue 16-DecJULIET
CART-BCMAU. Penn (rights to Novartis)1multiple myeloma16-Nov6 pts, 1 "€œstringent"€ CR, 1 PR, high toxicityNCT02546167
bb2121Bluebird (Celgene)1multiple myeloma16-Nov7 of 9 pts with response
2 "€œstringent"€ CR, 1 VGPR, 4 PR
BCMA CARNational Cancer Institute1multiple myeloma16-Sep12 pts, 2 VGPR, 1 stringent CR then relapse (17 wks)NCT02215967
(See p. 53)
two infants in CR, 1 adult deceasedcompassionate use
UCART-19Servier (Cellectis)1pediatric ALL16-Dec
(See p. 53)
2 pts: 1 CR (4 mo), 1 relapsed (6 mo) w/gr3 CRSPALL
UCART-19Servier (Cellectis)1adult ALL16-Dec
(See p. 53)
2 pts: 1 CR (4 mo), 1 deceasedCALM
NY-ESO TCRAdaptimmune1/2synovial sarcoma16-Oct7/20 OR across 4 cohorts
6/12 OR in cohort 1, median duration 31 wks
NY-ESO TCRAdaptimmune1/2multiple myeloma16-Jun3/22 CR (100 days)
20/22 OR (100 days)
NY-ESO TCRAdaptimmune1/2melanoma16-Jun0/4 ORNCT01350401
NY-ESO TCRAdaptimmune1/2ovarian cancer16-Jun0/6 ORNCT01567891
BPX-501Bellicum Pharma1/2BMT support for cancer, other blood diseases16-Dec
16/17 leukemia pts & 35/35 non-cancer pts "disease-free."€
Median follow-up 7 mo (cancer), 25-34 mo (non-cancer)
NKG2D CAR TCelyad1AML, myeloma16-Nov11 pts, 0-11 ORs after 28 days; 9 went to "subsequent therapies"NCT02203825
HER2-CARBaylor College of Medicine1Her2+ glioblastoma15-Nov8/16 ORR: 7 pts stable disease > 6 wks. Median OS 11.6 months from infusion.NCT01109095
HER2-CARBaylor College of Medicine1/2Her2+ sarcoma15-May19 pts. Median OS 10.3 mos. (Range 5.1 to 29.1 mos.)NCT00902044
CAR-K+Baylor College of Medicine1Lymphoma, myeloma, leukemia16-Jun9 NHL/CLL pts: 2 CR, 1 PR. 7 myeloma pts: 4 w/stable disease.NCT00881920
TIL + IL-2Lion Bio (NCI)1melanoma16-July101 pts: 24% CR in both arms.
Radiation: median OS 38.2 mo
No radiation: 36.6 mo

*JCAR014 is a non-commercial program that Juno has said is only intended for early clinical studies.
**Juno ended all JCAR015 development in March 2017.

Clinical terms
DFS: Disease-free survival. Length of time post-treatment the patient survives without sign of cancer.
PFS: Progression-free survival. Length of time post-treatment the patient survives without the cancer getting worse.
CR: Complete response, or complete remission: A patient’s cancer is undetectable.
OR: Objective response. A patient’s treatment has made a measurable effect on the cancer.
PR: Partial response. (VGPR = very good partial response.)
OS: Rate or percentage of people who survive after the start of treatment.
CRS: Cytokine release syndrome. A dangerous immune side effect triggered by T cell activity against cancer cells.

Disease and other abbreviations
ALL: Acute lymphocytic (or lymphoblastic) leukemia
AML: Acute myeloid leukemia
BMT: Bone marrow transplant
CLL: Chronic lymphocytic leukemia
NHL: Non-Hodgkin lymphoma. Subtypes include DLBCL (diffuse large B-cell lymphoma), PMBCL (primary mediastinal large B-cell lymphoma), and TFL (transformed follicular lymphoma).
NSCLC: Non small cell lung cancer

Photo of William Coley courtesy of The Wellcome Trust via Creative Commons.