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NCT04299048

Study to Assess the Safety and Tolerability of Repeated Doses of an Investigational New Drug in Patients With Cancer and Cachexia.

Completed Phase 1 Results posted Last updated 14 December 2023
What this trial tests

Phase 1 trial testing PF-06946860 in Cachexia in 11 participants. Completed in 30 March 2022.

Timeline
17 November 2020
Primary endpoint
30 March 2022
30 March 2022

Quick facts

Lead sponsorPfizer
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment11
Start date17 November 2020
Primary completion30 March 2022
Estimated completion30 March 2022
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Cachexia or Non-Small-Cell Lung Cancer. 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.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · From Day 1 up to Week 24

An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. An AE was considered an TEAE if the event started during the effective duration

AEs
GroupValue95% CI
PF-06946860 Q3W10
SAEs
GroupValue95% CI
PF-06946860 Q3W4
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Primary · From Day 1 up to Week 24

Participants with laboratory test abnormalities (without regard to baseline abnormality) that met pre-specified criteria included Hemoglobin\< 0.8x lower limit of normal (LLN); Hematocrit\< 0.8x LLN; Erythrocytes (Ery.)\< 0.8x LLN; Ery. Mean Corpuscular Volume\< 0.9x LLN; Leukocytes\< 0.6x LLN; Lymphocytes\< 0.8x LLN; Bilirubin\> 1.5x upper limit of normal (ULN); Aspartate Aminotransferase\> 3.0x ULN; Alkaline Phosphatase\> 3.0x ULN; Protein\< 0.8x LLN; Sodium\< 0.95x LLN; Chloride\< 0.9x LLN; Calcium\< 0.9x LLN; Bicarbonate\< 0.9x LLN; Glucose\> 1.5x ULN; C Reactive Protein\> 1.1x ULN; for ur

Hemoglobin (g/dL)< 0.8x LLN
GroupValue95% CI
PF-06946860 Q3W2
Hematocrit (%)< 0.8x LLN
GroupValue95% CI
PF-06946860 Q3W2
Erythrocytes (10^6/mm^3)< 0.8x LLN
GroupValue95% CI
PF-06946860 Q3W2
Ery. Mean Corpuscular Volume (um^3)< 0.9x LLN
GroupValue95% CI
PF-06946860 Q3W1
Leukocytes (10^3/mm^3)< 0.6x LLN
GroupValue95% CI
PF-06946860 Q3W2
Lymphocytes (10^3/mm^3)< 0.8x LLN
GroupValue95% CI
PF-06946860 Q3W3
Bilirubin (mg/dL)> 1.5x ULN
GroupValue95% CI
PF-06946860 Q3W1
Aspartate Aminotransferase (U/L)> 3.0x ULN
GroupValue95% CI
PF-06946860 Q3W1
Number of Participants With Post-Baseline Vital Signs Abnormalities Primary · From Day 1 up to Week 24

Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in vital signs, were supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg), supine SBP increase/decrease from baseline ≥30 mmHg; supine diastolic blood pressure (DBP) \<50 mmHg, supine DBP increase/decrease from baseline ≥20 mmHg; supine pulse rate \<40 beats per minute (bpm) or \>120 bpm.

Supine SBP - Value <90 mmHg
GroupValue95% CI
PF-06946860 Q3W0
Supine SBP - Change ≥ 30 mmHg Increase
GroupValue95% CI
PF-06946860 Q3W2
Supine SBP - Change ≥ 30 mmHg Decrease
GroupValue95% CI
PF-06946860 Q3W0
Supine DBP - Value <50 mmHg
GroupValue95% CI
PF-06946860 Q3W0
Supine DBP - Change ≥ 20 mmHg Increase
GroupValue95% CI
PF-06946860 Q3W1
Supine DBP - Change ≥ 20 mmHg Decrease
GroupValue95% CI
PF-06946860 Q3W0
Supine Pulse Rate - Value <40 bpm
GroupValue95% CI
PF-06946860 Q3W0
Supine Pulse Rate - Value >120 bpm
GroupValue95% CI
PF-06946860 Q3W0
Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities Primary · From Day 1 up to Week 24

ECG data (PR interval, QRS interval, QT interval, and QTcF) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in ECG, were PR interval: value ≥300 milliseconds (msec), percentage change ≥25/50%; QRS interval: value ≥140 msec, percentage change ≥50%; QT interval: value ≥500 msec; QTcF interval: 470\< value ≤480 msec, 480\< value ≤500 msec, value \>500 msec, and 30\< change ≤60 msec, change \>60 msec.

Supine PR Interval - Value ≥300 msec
GroupValue95% CI
PF-06946860 Q3W0
Supine PR Interval - %Chg ≥25/50%
GroupValue95% CI
PF-06946860 Q3W0
Supine QRS Interval - Value ≥140 msec
GroupValue95% CI
PF-06946860 Q3W0
Supine QRS Interval - %Chg ≥50%
GroupValue95% CI
PF-06946860 Q3W0
Supine QT Interval - Value ≥500 msec
GroupValue95% CI
PF-06946860 Q3W0
Supine QTcF - 470<Value≤480 msec
GroupValue95% CI
PF-06946860 Q3W0
Supine QTcF - 480<Value≤500 msec
GroupValue95% CI
PF-06946860 Q3W0
Supine QTcF - Value>500 msec
GroupValue95% CI
PF-06946860 Q3W0
Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 Secondary · Pre-dose at Weeks 3, 6, 9 and 12, and at Week 15

Ctrough was defined as the samples measured pre-dose at Weeks 3, 6, 9 and 12, and at Week 15. Serum unbound Ctrough was summarized by time and treatment group.

Week 3
GroupValue95% CI
PF-06946860 Q3W4.041± 1.28*10^19
Week 6
GroupValue95% CI
PF-06946860 Q3W1690± 593
Week 9
GroupValue95% CI
PF-06946860 Q3W610.9± 7.79*10^10
Week 12
GroupValue95% CI
PF-06946860 Q3W4383± 142
Week 15
GroupValue95% CI
PF-06946860 Q3W560.5± 2.15*10^12
Serum Total Ctrough of PF-06946860 Secondary · Pre-dose at Weeks 3, 6, 9 and 12, and at Week 15

Ctrough was defined as the samples measured pre-dose at Weeks 3, 6, 9 and 12, and at Week 15. Serum total Ctrough was summarized by time and treatment group.

Week 3
GroupValue95% CI
PF-06946860 Q3W10050± 19
Week 6
GroupValue95% CI
PF-06946860 Q3W17010± 16
Week 9
GroupValue95% CI
PF-06946860 Q3W20740± 24
Week 12
GroupValue95% CI
PF-06946860 Q3W21310± 32
Week 15
GroupValue95% CI
PF-06946860 Q3W25450± 31

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 1 up to Week 24. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-06946860 Q3W
Serious: 4/10 (40%)
Deaths: 1/10

Serious adverse events (5 terms)

ReactionSystemPF-06946860 Q3W
AnaemiaBlood and lymphatic system disorders
Cholecystitis acuteHepatobiliary disorders
SepsisInfections and infestations
Transaminases increasedInvestigations
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (63 terms — click to expand)

ReactionSystemPF-06946860 Q3W
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Lacrimation increasedEye disorders
Abdominal pain upperGastrointestinal disorders
VomitingGastrointestinal disorders
FallInjury, poisoning and procedural complications
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
InsomniaPsychiatric disorders
HypertensionVascular disorders
MonocytosisBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
ThrombocytosisBlood and lymphatic system disorders
Sinus tachycardiaCardiac disorders
HypothyroidismEndocrine disorders
Conjunctival hyperaemiaEye disorders
Abdominal discomfortGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Epigastric discomfortGastrointestinal disorders
Oral painGastrointestinal disorders
AstheniaGeneral disorders
COVID-19Infections and infestations
ConjunctivitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
Oral contusionInjury, poisoning and procedural complications
Skin lacerationInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
Electrocardiogram Q wave abnormalInvestigations
Decreased appetiteMetabolism and nutrition disorders

Most-reported serious reactions: Anaemia, Cholecystitis acute, Sepsis, Transaminases increased, Malignant neoplasm progression.

Data from ClinicalTrials.gov NCT04299048 adverse events section.

Sponsor's own description

Study to assess the safety and tolerability of repeated doses of an investigational new drug in patients with cancer and cachexia.

Publications & conference data

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

  1. Cancer cachexia: molecular mechanisms and treatment strategies.
    Setiawan T, Sari IN, Wijaya YT, Julianto NM, et al · · 2023 · cited 176× · PMID 37217930 · DOI 10.1186/s13045-023-01454-0
  2. Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.
    Haake M, Haack B, Schäfer T, Harter PN, et al · · 2023 · cited 76× · PMID 37474523 · DOI 10.1038/s41467-023-39817-3
  3. Role of growth differentiation factor 15 in cancer cachexia (Review).
    Ling T, Zhang J, Ding F, Ma L. · · 2023 · cited 45× · PMID 37780545 · DOI 10.3892/ol.2023.14049
  4. A Phase Ib First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia.
    Crawford J, Calle RA, Collins SM, Weng Y, et al · · 2024 · cited 39× · PMID 37982848 · DOI 10.1158/1078-0432.ccr-23-1631
  5. Current Therapeutic Targets in Cancer Cachexia: A Pathophysiologic Approach.
    Kadakia KC, Hamilton-Reeves JM, Baracos VE. · · 2023 · cited 38× · PMID 37290034 · DOI 10.1200/edbk_389942
  6. Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.
    Groarke JD, Crawford J, Collins SM, Lubaczewski SL, et al · · 2024 · cited 32× · PMID 38500292 · DOI 10.1002/jcsm.13435
  7. Cancer Cachexia: Signaling and Transcriptional Regulation of Muscle Catabolic Genes.
    Rao VK, Das D, Taneja R. · · 2022 · cited 14× · PMID 36077789 · DOI 10.3390/cancers14174258
  8. Cancer-triggered systemic disease and therapeutic targets.
    Cao Y. · · 2024 · cited 7× · PMID 38482486 · DOI 10.1007/s44178-024-00077-w

Verify or expand the search:

Other trials of PF-06946860

Trials testing the same drug.

Other recruiting trials for Cachexia

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

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