Trial Outcomes & Findings for Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers (NCT NCT02803203)
NCT ID: NCT02803203
Last Updated: 2023-09-22
Results Overview
The MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which \<1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
49 participants
Primary outcome timeframe
1 year
Results posted on
2023-09-22
Participant Flow
Participant milestones
| Measure |
Osimertinib and Bevacizumab
Phases 1+2: Osimertinib + Bevacizumab 80 mg Osimertinib PO QD and 15 mg/kg Bevacizumab IV Q3W
This section accurately reflects the flow of participants as all participants were enrolled into the same dosing cohort. This protocol utilized a dose de-escalation model where the initial dose was continued for Phase 2.
|
|---|---|
|
Overall Study
STARTED
|
49
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
49
|
Reasons for withdrawal
| Measure |
Osimertinib and Bevacizumab
Phases 1+2: Osimertinib + Bevacizumab 80 mg Osimertinib PO QD and 15 mg/kg Bevacizumab IV Q3W
This section accurately reflects the flow of participants as all participants were enrolled into the same dosing cohort. This protocol utilized a dose de-escalation model where the initial dose was continued for Phase 2.
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Death
|
4
|
|
Overall Study
Progressive disease
|
29
|
|
Overall Study
Withdrawal by Subject
|
8
|
|
Overall Study
Complete resection of target disease
|
2
|
|
Overall Study
Switched to commercial Osi
|
1
|
|
Overall Study
Participant moved away
|
1
|
Baseline Characteristics
Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers
Baseline characteristics by cohort
| Measure |
Osimertinib and Bevacizumab
n=49 Participants
Phases 1+2: Osimertinib + Bevacizumab 80 mg Osimertinib PO QD and 15 mg/kg Bevacizumab IV Q3W
This section accurately reflects the flow of participants as all participants were enrolled into the same dosing cohort. This protocol utilized a dose de-escalation model where the initial dose was continued for Phase 2.
|
|---|---|
|
Age, Continuous
|
60 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
46 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
14 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
49 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 1 yearThe MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which \<1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Outcome measures
| Measure |
Osimertinib and Bevacizumab
n=6 Participants
Phase 1 participants
|
|---|---|
|
Osimertinib Maximum Tolerated Dose (MTD) (Phase I)
|
80 mg
|
PRIMARY outcome
Timeframe: 1 yearThe MTD (maximum tolerated dose)/recommended phase 2 dose will be the highest dose level at which \<1 DLT is detected in the first cycle for 6 treated patients. If only 3 patients are treated at a dose level being considered for the MTD, an additional 3 patients will be enrolled.
Outcome measures
| Measure |
Osimertinib and Bevacizumab
n=6 Participants
Phase 1 participants
|
|---|---|
|
Bevacizumab Maximum Tolerated Dose (MTD) (Phase I)
|
15 mg/kg
|
PRIMARY outcome
Timeframe: 12 monthsTumor response will be assessed using RECIST 1.1. A CT chest/abdomen/pelvis will be performed to demonstrate all known areas of measurable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Osimertinib and Bevacizumab
n=49 Participants
Phase 1 participants
|
|---|---|
|
Progression-free Survival (Phase II)
Confirmed Partial Response/PR
|
34 Participants
|
|
Progression-free Survival (Phase II)
Unconfirmed Partial Response/PR
|
5 Participants
|
|
Progression-free Survival (Phase II)
Stable Disease/SD
|
9 Participants
|
|
Progression-free Survival (Phase II)
Not Evaluable/NE
|
1 Participants
|
Adverse Events
Osimertinib and Bevacizumab
Serious events: 26 serious events
Other events: 49 other events
Deaths: 37 deaths
Serious adverse events
| Measure |
Osimertinib and Bevacizumab
n=49 participants at risk
Phases 1+2: Osimertinib + Bevacizumab 80 mg Osimertinib PO QD and 15 mg/kg Bevacizumab IV Q3W
This section accurately reflects the flow of participants as all participants were enrolled into the same dosing cohort.
|
|---|---|
|
Cardiac disorders
Sinus tachycardia
|
2.0%
1/49 • 1 year
|
|
Cardiac disorders
Ventricular tachycardia
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Esophagitis
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify: Cholangitis
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
4.1%
2/49 • 1 year
|
|
General disorders
Edema limbs
|
2.0%
1/49 • 1 year
|
|
General disorders
Fever
|
8.2%
4/49 • 1 year
|
|
General disorders
Non-cardiac chest pain
|
6.1%
3/49 • 1 year
|
|
General disorders
Sudden death NOS
|
2.0%
1/49 • 1 year
|
|
Infections and infestations
Infections and infestations - Other, specify: Thyroid Gland
|
2.0%
1/49 • 1 year
|
|
Infections and infestations
Lung infection
|
8.2%
4/49 • 1 year
|
|
Infections and infestations
Sepsis
|
2.0%
1/49 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
1/49 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.1%
2/49 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms ben/mal/unk (inc cyst/polyp) Other, spec
|
4.1%
2/49 • 1 year
|
|
Nervous system disorders
Facial nerve disorder
|
2.0%
1/49 • 1 year
|
|
Nervous system disorders
Headache
|
6.1%
3/49 • 1 year
|
|
Nervous system disorders
Lethargy
|
2.0%
1/49 • 1 year
|
|
Nervous system disorders
Seizure
|
2.0%
1/49 • 1 year
|
|
Nervous system disorders
Stroke
|
6.1%
3/49 • 1 year
|
|
Psychiatric disorders
Confusion
|
4.1%
2/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.0%
1/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.2%
4/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
6.1%
3/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
6.1%
3/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.0%
1/49 • 1 year
|
|
Renal and urinary disorders
Proteinuria
|
8.2%
4/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.0%
1/49 • 1 year
|
|
Vascular disorders
Hypertension
|
4.1%
2/49 • 1 year
|
|
Vascular disorders
Hypotension
|
2.0%
1/49 • 1 year
|
|
Vascular disorders
Thromboembolic event
|
2.0%
1/49 • 1 year
|
|
Nervous system disorders
Dizziness
|
2.0%
1/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Gastric ulcer
|
2.0%
1/49 • 1 year
|
|
Vascular disorders
Vascular disorders - Other
|
2.0%
1/49 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
2.0%
1/49 • 1 year
|
|
Cardiac disorders
Pericardial effusion
|
2.0%
1/49 • 1 year
|
Other adverse events
| Measure |
Osimertinib and Bevacizumab
n=49 participants at risk
Phases 1+2: Osimertinib + Bevacizumab 80 mg Osimertinib PO QD and 15 mg/kg Bevacizumab IV Q3W
This section accurately reflects the flow of participants as all participants were enrolled into the same dosing cohort.
|
|---|---|
|
Investigations
Alanine aminotransferase increased
|
8.2%
4/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.1%
3/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
6.1%
3/49 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
20.4%
10/49 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.4%
10/49 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
18.4%
9/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.1%
3/49 • 1 year
|
|
Investigations
CPK increased
|
38.8%
19/49 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
100.0%
49/49 • 1 year
|
|
Nervous system disorders
Dizziness
|
8.2%
4/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
46.9%
23/49 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
10.2%
5/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.2%
4/49 • 1 year
|
|
General disorders
Edema limbs
|
18.4%
9/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
38.8%
19/49 • 1 year
|
|
General disorders
Fatigue
|
81.6%
40/49 • 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
6.1%
3/49 • 1 year
|
|
General disorders
Gen disorders & admin site conditions Other
|
44.9%
22/49 • 1 year
|
|
Nervous system disorders
Headache
|
10.2%
5/49 • 1 year
|
|
Renal and urinary disorders
Hematuria
|
6.1%
3/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
24.5%
12/49 • 1 year
|
|
Vascular disorders
Hypertension
|
100.0%
49/49 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.1%
3/49 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
100.0%
49/49 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
81.6%
40/49 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
24.5%
12/49 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
6.1%
3/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
22.4%
11/49 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
55.1%
27/49 • 1 year
|
|
Investigations
Neutrophil count decreased
|
16.3%
8/49 • 1 year
|
|
Nervous system disorders
Paresthesia
|
6.1%
3/49 • 1 year
|
|
Infections and infestations
Paronychia
|
32.7%
16/49 • 1 year
|
|
Investigations
Platelet count decreased
|
100.0%
49/49 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
6.1%
3/49 • 1 year
|
|
Renal and urinary disorders
Proteinuria
|
100.0%
49/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.3%
7/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
67.3%
33/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
53.1%
26/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue disorders Other
|
6.1%
3/49 • 1 year
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
8.2%
4/49 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
16.3%
8/49 • 1 year
|
|
Investigations
Weight loss
|
24.5%
12/49 • 1 year
|
|
Investigations
White blood cell decreased
|
83.7%
41/49 • 1 year
|
Additional Information
Dr. Helena Yu, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-608-3912
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place