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NCT02298946

AMP-224, a PD-1 Inhibitor, With Stereotactic Body Radiation Therapy in Metastatic Colorectal Cancer

Completed Phase 1 Results posted Last updated 22 February 2019
What this trial tests

Phase 1 trial testing AMP-224 in Colorectal Cancer in 17 participants. Completed in 7 March 2017.

Timeline
21 November 2014
Primary endpoint
13 July 2016
7 March 2017

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment17
Start date21 November 2014
Primary completion13 July 2016
Estimated completion7 March 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Colorectal Cancer or Colorectal Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Primary · Date treatment consent signed to date off study, approximately 24 months and 8 days

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one o

GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2246
DL2 - CTX, SBRTx3 Days, and AMP-2249
Number of Participants in Which Specimens Were Collected for Pre and Post Pharmacokinetic (PK) AMP-224 Analyses Secondary · Baseline and post infusion AMP-224 (e.g. 15 minutes after infusion ended)

This outcome measure only represents the number of participants with metastatic colorectal cancer who had specimens collected for pre and post pharmacokinetic (PK) AMP-224 analyses.

Pre AMP-224
GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2246
DL2 - CTX, SBRTx3 Days, and AMP-2249
Post AMP-224
GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2246
DL2 - CTX, SBRTx3 Days, and AMP-2249
Overall Survival in Patients With Colorectal Cancer Following Treatment With AMP-224 in Combination With SBRT Secondary · Baseline to end of study, which is date of death. Average time participants were followed was 10.6 months.

Overall survival is defined as the time from treatment start date until date of death or date last known alive.

GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2244.31.2 – 8.9
DL2 - CTX, SBRTx3 Days, and AMP-2249.01.5 – 21.3
Count of Participants With Post-Treatment Biopsies Secondary · Post treatment, day 29 +/- 7 days

Mandatory post treatment biopsies of the tumor were attempted on all patients.

GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2246
DL2 - CTX, SBRTx3 Days, and AMP-2240
Median Progression-free Survival in Patients With Colorectal Cancer Secondary · Baseline to disease progression, an average of 2.6 months.

Progression free survival is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also con

GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2241.70.9 – 3.3
DL2 - CTX, SBRTx3 Days, and AMP-2242.70.3 – 12.8
Objective Response Rate Secondary · Restaging was done every 8 weeks for an average of 2.6 months.

Objective response will be evaluated according to the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and is defined as Complete Response + Partial Response. Briefly, complete response (CR) is defined as the disappearance of all target lesions, and Partial Response is defined as "at least" 30% decrease in the sum of the diameters of the target lesions from baseline measurement.

GroupValue95% CI
DL1 - CTX, SBRTx1 Day, & AMP-2240
DL2 - CTX, SBRTx3 Days, and AMP-2240

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 24 months and 8 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DL1 - CTX, SBRTx1 Day, & AMP-224
Serious: 4/6 (67%)
Deaths: 6/6
DL2 - CTX, SBRTx3 Days, and AMP-224
Serious: 2/9 (22%)
Deaths: 9/9

Serious adverse events (7 terms)

ReactionSystemDL1 - CTX, SBRTx1 Day, & A…DL2 - CTX, SBRTx3 Days, an…
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
ConfusionPsychiatric disorders
Death NOSGeneral disorders
DehydrationMetabolism and nutrition disorders
HeadacheNervous system disorders
HyperuricemiaMetabolism and nutrition disorders
Other adverse events (59 terms — click to expand)

ReactionSystemDL1 - CTX, SBRTx1 Day, & A…DL2 - CTX, SBRTx3 Days, an…
Activated partial thromboplastin time prolongedInvestigations
AnemiaBlood and lymphatic system disorders
Lymphocyte count decreasedInvestigations
Alkaline phosphatase increasedInvestigations
FatigueGeneral disorders
HypoalbuminemiaMetabolism and nutrition disorders
Infusion related reactionGeneral disorders
PainGeneral disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Blood bilirubin increasedInvestigations
DiarrheaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
HeadacheNervous system disorders
HyperuricemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
Serum amylase increasedInvestigations
Urinary tract infectionInfections and infestations
White blood cell decreasedInvestigations
AnxietyPsychiatric disorders
Blurred visionEndocrine disorders
Chest pain - cardiacCardiac disorders
ChillsGeneral disorders
Cholesterol highInvestigations
Cognitive disturbanceNervous system disorders
ConfusionPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
Creatinine increasedInvestigations
DehydrationMetabolism and nutrition disorders
DizzinessNervous system disorders
Edema limbsGeneral disorders
FeverGeneral disorders

Most-reported serious reactions: Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify, Adult respiratory distress syndrome, Confusion, Death NOS, Dehydration, Headache, Hyperuricemia.

Data from ClinicalTrials.gov NCT02298946 adverse events section.

Sponsor's own description

Background: \- T-cells are white blood cells that can find and kill germs and tumors. Cancer can keep T-cells from working. Researchers think a new drug called AMP-224 might help the T-cells in people with cancer. They think the drug might work even better when combined with a certain type of radiation therapy. Objective: \- To study the safety and effectiveness of AMP-224 together with 1 or 3 days of stereotactic body radiation therapy (SBRT) directed to the liver. Eligibility: \- People age 18 and older with metastatic colorectal cancer. Their cancer must have spread to the liver and not be responding to treatment. Design: * Participants will be screened with a medical history, physical exam, and blood and urine tests. Their tumors will be measured with computerized tomography (CT) scans or magnetic resonance imaging (MRI) of the chest, stomach, and pelvis. They will have an electrocardiogram (ECG) heart test. * Participants will have a small part of their tumor removed by needle (biopsy). * Participants will have 8 study visits over about 10 weeks. * At 1 visit, they will have another tumor biopsy. * At 1 visit, they will get a chemotherapy drug through a vein (intravenous (IV)). * At 6 visits, they will receive AMP-224 through an IV. * At 1 or 3 visits, they will have SBRT. Computed tomography (CT) scans will map the position of their tumor. Radiation beams of different intensities at different angles will be directed to the tumor. * At all visits, some screening procedures may be repeated. * After treatment ends, participants will have 7 follow-up visits over about 5 months. Blood will be drawn. Some screening procedures may be repeated.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
    Alsaab HO, Sau S, Alzhrani R, Tatiparti K, et al · · 2017 · cited 1206× · PMID 28878676 · DOI 10.3389/fphar.2017.00561
  2. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  3. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?
    Bernstein MB, Krishnan S, Hodge JW, Chang JY. · · 2016 · cited 325× · PMID 26951040 · DOI 10.1038/nrclinonc.2016.30
  4. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.
    Pol J, Vacchelli E, Aranda F, Castoldi F, et al · · 2015 · cited 238× · PMID 26137404 · DOI 10.1080/2162402x.2015.1008866
  5. Review of PD-1/PD-L1 Inhibitors in Metastatic dMMR/MSI-H Colorectal Cancer.
    Oliveira AF, Bretes L, Furtado I. · · 2019 · cited 152× · PMID 31139574 · DOI 10.3389/fonc.2019.00396
  6. Radiation-induced neoantigens broaden the immunotherapeutic window of cancers with low mutational loads.
    Lussier DM, Alspach E, Ward JP, Miceli AP, et al · · 2021 · cited 109× · PMID 34099555 · DOI 10.1073/pnas.2102611118
  7. Immunotherapy for Colorectal Cancer.
    Boland PM, Ma WW. · · 2017 · cited 105× · PMID 28492495 · DOI 10.3390/cancers9050050
  8. Harnessing the immune system against cancer: current immunotherapy approaches and therapeutic targets.
    Kumar AR, Devan AR, Nair B, Vinod BS, et al · · 2021 · cited 98× · PMID 34671902 · DOI 10.1007/s11033-021-06752-9

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02298946.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing