Cachexia, Colorectal Cancer, Non-Small-Cell Lung Cancer, Pancreatic Cancer
Conditions
Keywords
cachexia, non-small cell lung cancer, pancreatic cancer, colorectal cancer, weight loss, anorexia, muscle loss, fatigue
Brief summary
Study to assess the safety and tolerability of repeated doses of an investigational new drug in patients with cancer and cachexia.
Detailed description
This 12-week open-label study will explore how PF-06946860 is tolerated, the effects of the study drug, the best dose for treatment and how participants with non-small cell lung, pancreatic or colorectal cancer and cachexia feel after receiving repeated subcutaneous dosing. During the 12-week treatment period, study drug will be administered subcutaneously every 3 weeks for a total of 5 doses. There is a 12-week follow-up period following the last dose of study drug. Additional assessments include: * body weight measurements * blood pressure and heart rate measurements * Lumbar Skeletal Muscle Index (LSMI) by CT scan * Blood samples: * to evaluate safety, * to measure the amount of the study drug in the blood, * to evaluate if the study drug causes an immune response, * to examine the effects of the study drug on levels of a specific cytokine, * and for exploratory samples for bio banking. * Measure the impact of the study drug on appetite, nausea, vomiting, fatigue, physical function, and health-related quality of life with questionnaires. * Measure the impact of study drug on physical activity using wearable digital sensors. * To evaluate the effect of study drug on ability to complete anti-tumor treatment and survival in participants with cancer and cachexia. * To evaluate tumor size.
Interventions
DRUGPF-06946860
subcutaneous injection
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented histologic or cytologic diagnosis of advanced metastatic NSCLC, advanced/unresectable pancreatic cancer, or metastatic colorectal cancer. * Cachexia, defined by BMI \<20 kg/m2 with involuntary weight loss of \>2% within 6 months prior to screening or Involuntary weight loss of \>5% within 6 months prior to screening irrespective of BMI or If medical record documentation is unavailable, patient's report will suffice to estimate involuntary body weight loss.; * Will receive the following for non-small cell lung cancer: * a platinum + pemetrexed ± pembrolizumab or * a platinum + nab paclitaxel or paclitaxel ± pembrolizumab or * pembrolizumab alone * Will receive the following for pancreatic cancer: * FOLFIRINOX or * Nab-Paclitaxel + Gemcitabine * Gemcitabine * Will receive the following for colorectal cancer: * FOLFOX +/- Biologic (Bevacizumab or Cetuximab/Panitumumab) or * FOLFIRI +/- Biologic (Bevacizumab or Cetuximab/Panitumumab) or * FOLFOXIRI +/- Biologic (Bevacizumab or Cetuximab/Panitumumab) or * Pembrolizumab for MSI-H • Will be entering the study at the first or second cycle of their current course of anti-cancer treatment/ therapy. * Adequate renal and liver function. * Signed informed consent.
Exclusion criteria
* All other forms of cancers not specified above unless currently considered cured (\>5 years without evidence of recurrence). * Planned radiation therapy as part of the primary anti-tumor therapy regimen. However, localized radiation therapy for symptomatic relief is permitted * Cachexia caused by other reasons: Severe COPD requiring use of home O2, heart failure or AIDS. * known symptomatic brain metastases requiring steroids. * Active hepatitis B or C virus. * Confirmed positive HIV test. * Current active reversible causes of decreased food intake. * Receiving tube feedings or parenteral nutrition at Screening. * Elevated blood pressure that cannot be controlled by medications. * Women who are pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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 of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 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 urinalysis, Urine Glucose ≥1, Ketones ≥1, Urine Protein ≥1, Urine Hemoglobin ≥1, Urobilinogen ≥1, Nitrite ≥1, and Leukocyte ≥1 Esterase ≥1; Hyaline Casts \>1/LPF. |
| Number of Participants With Post-Baseline Vital Signs Abnormalities | 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. |
| Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 | 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. |
| Serum Total Ctrough of PF-06946860 | 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 20 participants were screened for eligibility, of which 11 participants were enrolled into the study. A total of 10 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| PF-06946860 Q3W During the 12-week treatment period, participants receive a total of 5 SC doses of PF-06946860 Q3W. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Enrolled and not treated | 1 |
| Overall Study | Global deterioration of health status | 2 |
Baseline characteristics
| Characteristic | PF-06946860 Q3W |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Body Mass Index | 22.88 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
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 urinalysis, Urine Glucose ≥1, Ketones ≥1, Urine Protein ≥1, Urine Hemoglobin ≥1, Urobilinogen ≥1, Nitrite ≥1, and Leukocyte ≥1 Esterase ≥1; Hyaline Casts \>1/LPF.
Time frame: From Day 1 up to Week 24
Population: Overall number of participants analyzed included participants with at least one observation of the given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Aspartate Aminotransferase (U/L)> 3.0x ULN | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Alkaline Phosphatase (U/L)> 3.0x ULN | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Protein (g/dL)< 0.8x LLN | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Sodium (mEq/L)< 0.95x LLN | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Chloride (mEq/L)< 0.9x LLN | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Calcium (mg/dL)< 0.9x LLN | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Bicarbonate (mEq/L)< 0.9x LLN | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Glucose (mg/dL)> 1.5x ULN | 4 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | C Reactive Protein (mg/dL)> 1.1x ULN | 5 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINE Glucose ≥1 | 3 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Ketones ≥1 | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINE Protein ≥1 | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin ≥1 | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen ≥1 | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Nitrite ≥1 | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Leukocyte Esterase ≥1 | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hyaline Casts >1/LPF | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hemoglobin (g/dL)< 0.8x LLN | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematocrit (%)< 0.8x LLN | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Erythrocytes (10^6/mm^3)< 0.8x LLN | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (um^3)< 0.9x LLN | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Leukocytes (10^3/mm^3)< 0.6x LLN | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Lymphocytes (10^3/mm^3)< 0.8x LLN | 3 Participants |
| PF-06946860 Q3W | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL)> 1.5x ULN | 1 Participants |
Primary
Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities
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.
Time frame: From Day 1 up to Week 24
Population: Overall number of participants analyzed included participants evaluated against pre-defined criteria for ECGs.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine PR Interval - Value ≥300 msec | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine PR Interval - %Chg ≥25/50% | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QRS Interval - Value ≥140 msec | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QRS Interval - %Chg ≥50% | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QT Interval - Value ≥500 msec | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QTcF - 470<Value≤480 msec | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QTcF - 480<Value≤500 msec | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QTcF - Value>500 msec | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QTcF - 30<Chg≤60 msec | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities | Supine QTcF - Chg>60 msec | 0 Participants |
Primary
Number of Participants With Post-Baseline Vital Signs Abnormalities
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.
Time frame: From Day 1 up to Week 24
Population: Overall number of participants analyzed included participants evaluated against pre-defined criteria for vital signs.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine SBP - Value <90 mmHg | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine SBP - Change ≥ 30 mmHg Increase | 2 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine SBP - Change ≥ 30 mmHg Decrease | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine DBP - Value <50 mmHg | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine DBP - Change ≥ 20 mmHg Increase | 1 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine DBP - Change ≥ 20 mmHg Decrease | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine Pulse Rate - Value <40 bpm | 0 Participants |
| PF-06946860 Q3W | Number of Participants With Post-Baseline Vital Signs Abnormalities | Supine Pulse Rate - Value >120 bpm | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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 of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs.
Time frame: From Day 1 up to Week 24
Population: The safety analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06946860 Q3W | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | AEs | 10 Participants |
| PF-06946860 Q3W | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 4 Participants |
Secondary
Serum Total Ctrough of PF-06946860
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.
Time frame: Pre-dose at Weeks 3, 6, 9 and 12, and at Week 15
Population: The analysis set included all randomized participants who received a dose of PF-06946860 and in whom at least 1 serum concentration value was reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06946860 Q3W | Serum Total Ctrough of PF-06946860 | Week 3 | 10050 ng/mL | Geometric Coefficient of Variation 19 |
| PF-06946860 Q3W | Serum Total Ctrough of PF-06946860 | Week 6 | 17010 ng/mL | Geometric Coefficient of Variation 16 |
| PF-06946860 Q3W | Serum Total Ctrough of PF-06946860 | Week 9 | 20740 ng/mL | Geometric Coefficient of Variation 24 |
| PF-06946860 Q3W | Serum Total Ctrough of PF-06946860 | Week 12 | 21310 ng/mL | Geometric Coefficient of Variation 32 |
| PF-06946860 Q3W | Serum Total Ctrough of PF-06946860 | Week 15 | 25450 ng/mL | Geometric Coefficient of Variation 31 |
Secondary
Serum Unbound Trough Concentrations (Ctrough) of PF-06946860
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.
Time frame: Pre-dose at Weeks 3, 6, 9 and 12, and at Week 15
Population: The analysis set included all randomized participants who received a dose of PF-06946860 and in whom at least 1 serum concentration value was reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06946860 Q3W | Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 | Week 3 | 4.041 ng/mL | — |
| PF-06946860 Q3W | Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 | Week 6 | 1690 ng/mL | Geometric Coefficient of Variation 593 |
| PF-06946860 Q3W | Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 | Week 9 | 610.9 ng/mL | — |
| PF-06946860 Q3W | Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 | Week 12 | 4383 ng/mL | Geometric Coefficient of Variation 142 |
| PF-06946860 Q3W | Serum Unbound Trough Concentrations (Ctrough) of PF-06946860 | Week 15 | 560.5 ng/mL | — |