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Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor
Phase 1 trial testing Pembrolizumab in Advanced Solid Tumor in 62 participants. Completed in 13 December 2024.
| Lead sponsor | Dana-Farber Cancer Institute |
|---|---|
| Phase | Phase 1 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | non randomized |
| Design | parallel |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 62 |
| Start date | 1 May 2018 |
| Primary completion | 13 December 2024 |
| Estimated completion | 13 December 2024 |
| Sites | 2 locations across United States |
Dana-Farber Cancer Institute
18 and older, any sex, with Advanced Solid Tumor. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
A standard 3+3 dose-escalation design was used during dose escalation period. DLT was defined in protocol section 5.5.
| Group | Value | 95% CI |
|---|---|---|
| [Dose Escalation Dose Level I] Pembrolizumab + Trebananib | 0 | |
| [Dose Escalation Dose Level II] Pembrolizumab + Trebananib | 0 |
MTD will be defined as the dose level at which fewer than one-third of participants experience a dose-limiting toxicity attributable to pembrolizumab and trebananib, as determined using a standard 3+3 dose-escalation design.
| Group | Value | 95% CI |
|---|---|---|
| [Dose Escalation Dose Level I and Dose Level II] Pembrolizumab + Trebananib | 30 |
The percentage of participants who experienced grade 3 or higher event based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4).
| Group | Value | 95% CI |
|---|---|---|
| [Dose Expansion Dose Level II] Pembrolizumab + Trebananib (Colorectal) | 59.5 | 44.6 – 73.1 |
| Dose Expansion Dose Level II] Pembrolizumab + Trebananib (Ovarian) | 63.6 | 35.0 – 86.5 |
| Dose Expansion Dose Level II] Pembrolizumab + Trebananib (Renal Cell Carcinoma) | 75.0 | 24.9 – 98.7 |
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
| Group | Value | 95% CI |
|---|---|---|
| [Dose Level II] Pembrolizumab + Trebananib (Colorectal) | 7.5 | 2.1 – 18.3 |
| [Dose Level II] Pembrolizumab + Trebananib (Ovarian) | 9.1 | 0.1 – 36.4 |
| [Dose Level II] Pembrolizumab + Trebananib (Renal Cell Carcinoma) | 0 | 0 – 52.7 |
PFS6 is the percent probability estimate at 6 months based on the Kaplan-Meier method. PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal
| Group | Value | 95% CI |
|---|---|---|
| [Dose Level II] Pembrolizumab + Trebananib (Colorectal) | 13 | 5 – 25 |
| [Dose Level II] Pembrolizumab + Trebananib (Ovarian) | 9 | 1 – 33 |
| [Dose Level II] Pembrolizumab + Trebananib (Renal Cell Carcinoma) | 50 | 6 – 84 |
OS1 is the percent probability estimate at 1 year based on the Kaplan-Meier method. O is defined as the time from start of trial treatment to death from any cause. For patients who are lost to follow-up or who have no documentation of death at the time of final analysis, follow-up will be censored at the date of last assessment of vital status. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on e
| Group | Value | 95% CI |
|---|---|---|
| [Dose Level II] Pembrolizumab + Trebananib (Colorectal) | 45 | 28 – 61 |
| [Dose Level II] Pembrolizumab + Trebananib (Ovarian) | 80 | 38 – 95 |
| [Dose Level II] Pembrolizumab + Trebananib (Renal Cell Carcinoma) | 50 | 6 – 84 |
TTP based on Kaplan-Meier method is defined as the time interval between the dates of the start of trial treatment and first documentation of progressive disease. In the absence of documented progressive disease, follow-up would be censored at date of last disease assessment. Deaths without prior progression would be censored events.
| Group | Value | 95% CI |
|---|---|---|
| [Dose Level II] Pembrolizumab + Trebananib (Colorectal) | 3.1 | 2.8 – 3.2 |
| [Dose Level II] Pembrolizumab + Trebananib (Ovarian) | 3.1 | 3.0 – 3.8 |
| [Dose Level II] Pembrolizumab + Trebananib (Renal Cell Carcinoma) | 4.4 | 1.2 – NA |
Time frame: The median is 3.3 months (range: 0.6 to 25.3 months). Survival status was followed up to 60 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | [Dose Level I] Pembrolizum… | [Dose Expansion Dose Level… | Dose Expansion Dose Level … | Dose Expansion Dose Level … |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | — | — | — | — |
| Fever | General disorders and administration site conditions | — | — | — | — |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| Anemia | Blood and lymphatic system disorders | — | — | — | — |
| Pericardial effusion | Cardiac disorders | — | — | — | — |
| Colitis | Gastrointestinal disorders | — | — | — | — |
| Diarrhea | Gastrointestinal disorders | — | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — | — |
| Edema limbs | General disorders and administration site conditions | — | — | — | — |
| Localized edema | General disorders and administration site conditions | — | — | — | — |
| Biliary tract infection | Infections and infestations | — | — | — | — |
| Lung infection | Infections and infestations | — | — | — | — |
| Sepsis | Infections and infestations | — | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — | — |
| Alkaline phosphatase increased | Investigations | — | — | — | — |
| Aspartate aminotransferase increased | Investigations | — | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — | — |
| GGT increased | Investigations | — | — | — | — |
| Lipase increased | Investigations | — | — | — | — |
| Hyponatremia | Metabolism and nutrition disorders | — | — | — | — |
| Headache | Nervous system disorders | — | — | — | — |
| Syncope | Nervous system disorders | — | — | — | — |
| Acute kidney injury | Renal and urinary disorders | — | — | — | — |
| Urinary retention | Renal and urinary disorders | — | — | — | — |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| Reaction | System | [Dose Level I] Pembrolizum… | [Dose Expansion Dose Level… | Dose Expansion Dose Level … | Dose Expansion Dose Level … |
|---|---|---|---|---|---|
| Alkaline phosphatase increased | Investigations | — | — | — | — |
| Anemia | Blood and lymphatic system disorders | — | — | — | — |
| Aspartate aminotransferase increased | Investigations | — | — | — | — |
| Fatigue | General disorders and administration site conditions | — | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — | — |
| Proteinuria | Renal and urinary disorders | — | — | — | — |
| Hyponatremia | Metabolism and nutrition disorders | — | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — | — |
| Hypoalbuminemia | Metabolism and nutrition disorders | — | — | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — | — | — |
| Hypothyroidism | Endocrine disorders | — | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — | — |
| Lipase increased | Investigations | — | — | — | — |
| Activated partial thromboplastin time prolonged | Investigations | — | — | — | — |
| Hyperthyroidism | Endocrine disorders | — | — | — | — |
| Diarrhea | Gastrointestinal disorders | — | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — | — |
| Serum amylase increased | Investigations | — | — | — | — |
| Hypophosphatemia | Metabolism and nutrition disorders | — | — | — | — |
| Fever | General disorders and administration site conditions | — | — | — | — |
| Anorexia | Metabolism and nutrition disorders | — | — | — | — |
| Hematuria | Renal and urinary disorders | — | — | — | — |
| Pruritus | Skin and subcutaneous tissue disorders | — | — | — | — |
| Abdominal distension | Gastrointestinal disorders | — | — | — | — |
| Edema limbs | General disorders and administration site conditions | — | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — | — |
| Creatinine increased | Investigations | — | — | — | — |
| Neutrophil count decreased | Investigations | — | — | — | — |
| Platelet count decreased | Investigations | — | — | — | — |
| Hyperglycemia | Metabolism and nutrition disorders | — | — | — | — |
| Arthralgia | Musculoskeletal and connective tissue disorders | — | — | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| Chills | General disorders and administration site conditions | — | — | — | — |
| INR increased | Investigations | — | — | — | — |
| Dehydration | Metabolism and nutrition disorders | — | — | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — | — | — |
| Pain in extremity | Musculoskeletal and connective tissue disorders | — | — | — | — |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| Sinus tachycardia | Cardiac disorders | — | — | — | — |
| Dry mouth | Gastrointestinal disorders | — | — | — | — |
Most-reported serious reactions: Abdominal pain, Fever, Pneumonitis, Anemia, Pericardial effusion, Colitis, Diarrhea, Vomiting.
Data from ClinicalTrials.gov NCT03239145 adverse events section.
This research study is studying an investigational combination of drugs as a possible treatment for advanced solid tumors: melanoma, ovarian, renal, or colorectal cancer. The drugs involved in this study are: * Pembrolizumab * AMG386
8 peer-reviewed publications reference this trial (live from Europe PMC):
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