Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MEDI9447 (oleclumab), Oleclumab
MEDI9447 · 5 trials · 6 indications
PFS12 is defined as the Kaplan-Meier estimate of PFS at 12 months per RECIST 1.1 as assessed by the investigator.
To assess the safety and tolerability, describe any dose-limiting toxicity (DLT) for MEDI9447
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
DLT: Any study drug related Grade (G)3 or higher toxicity including: any G4 immune-mediated AEs, \>=G3 colitis/pneumonitis/interstitial lung disease (ILD), \>=G3 nausea/vomiting/diarrhea that does not resolve to G2 or less within 3 days of maximal supportive care (MSC), G2 pneumonitis/ILD that does not resolve within 7 days of initiation of MSC, G4 anemia, G3 anemia with clinical sequelae/requires \>2 units of red blood cells transfusion, G4 thrombocytopenia/neutropenia \>=7 days, G3/4 thrombocytopenia with \>=G3 hemorrhage, G4 febrile neutropenia (FN), G3 FN lasting \>=5 days while receiving MSC, isolated G3 liver transaminase elevation (LTE)/ isolated G3 total bilirubin (TBL) that does not downgrade to G1 or less within 14 days of onset, isolated G4 LTE or TBL, elevated aspartate aminotransferase/alanine aminotransferase \>3×upper limit of normal (ULN) and concurrent TBL \>2×ULN without cholestasis or alternative explanations, any other toxicity judged as a DLT by Dose Escalation Committee.
Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.
Number of participants with abnormal ECG parameters reported as TEAEs are reported.
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs), any pathological lymph nodes (target and non-target) must have reduction in short axis \< 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported.
A DLT was defined as \>= Grade 3 toxicity or adverse events (AE) occurred during DLT evaluation period which included any Grade 4 immune-mediated (immune nature) AE, anemia, thrombocytopenia (present \> 4 days), or neutropenia (present \> 4 days); \>= Grade 3 colitis or pneumonitis or interstitial lung disease (ILD); \>= Grade 3 nausea, vomiting, or diarrhea (not resolved to \<= Grade 2 in 3 days); Grade 2 pneumonitis or ILD (not resolved to \<= Grade 1 in 3 days); Grade 3 thrombocytopenia with bleeding, any grade febrile neutropenia; convulsions, seizures, or stroke; protocol defined elevations of isolated liver transaminase, isolated total bilirubin (TBL), or Hy's Law; confirmed QT interval corrected for heart rate by Fridericia's formula prolongation (\>= 501 msec) on triplicate electrocardiograms within a short period of time; or any other toxicity greater than that at baseline, was clinically significant and/or unacceptable, and was judged to be a DLT by the Dose Escalation Committee.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, and urinalysis.
Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) and physical examination reported as TEAEs are reported.
Notable QTc intervals included single beat changes from baseline (Day 1) values (\> 30, \> 60, and \> 90 milliseconds). Participants who had notable QTc interval are reported.
The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and non-progressive disease and not evaluable or no non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.
A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period, which included any Grade 4 immune-mediated adverse event (imAE), any \>= Grade 3 colitis, any Grade 3 or 4 non-infectious pneumonitis irrespective of duration, any Grade 3 imAE (excluding colitis or pneumonitis, did not downgrade to \<= Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or did not downgrade to \<= Grade 1 or baseline within 14 days), liver transaminase elevation \>= 5 × but \<= 8 × upper limit of normal (ULN) that did not downgrade to Grade 2 within 5 days after onset with optimal medical management (including systemic corticosteroids), transaminase elevation \> 8 × ULN or total bilirubin (TBL) \> 5 × ULN regardless of duration or reversibility, or any increase in aspartate aminotransferase or alanine aminotransferase \> 3 × ULN and concurrent increase in TBL \> 2 × ULN (Hy's Law).
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, coagulation, and urinalysis.
Participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.
Number of participants with change from Baseline in QTcF (\> 60 msec and \> 90 msec) is reported.
| Arm | Type | Description |
|---|---|---|
| Arm 1 | EXPERIMENTAL | durvalumab plus oleclumab as an IV infusions |
| MEDI9447 monotherapy | OTHER | Dose escalation of MEDI9447 monotherapy for patients with advanced solid malignancies |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel | EXPERIMENTAL | Participants with 1L metastatic disease will receive intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel | EXPERIMENTAL | Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | EXPERIMENTAL | Participants with 2L metastatic disease will receive IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m\^2 IV; folinic acid 400 mg/m\^2 IV; 5-FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | EXPERIMENTAL | Participants with 2L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m\^2 IV; folinic acid 400 mg/m\^2 IV; 5-FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Dose-expansion, Gemcitabine + nab-paclitaxel | ACTIVE_COMPARATOR | Participants with 1L metastatic disease will receive IV infusions of chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel | EXPERIMENTAL | Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel | EXPERIMENTAL | Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met. |
| Oleclumab Dose 1 + Osimertinib Dose 1 | EXPERIMENTAL | In Part 1 (dose-escalation), participants will receive intravenous oleclumab (MEDI9447) Dose 1 every 2 weeks (Q2W) and oral osimertinib Dose 1 once daily (QD). |
| Oleclumab Dose 2 + Osimertinib Dose 1 | EXPERIMENTAL | In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 2 Q2W and oral osimertinib Dose 1 QD. In Part 2 (dose-expansion), participants (including participants dosed at the RP2D in Part 1) will receive IV oleclumab Dose 2 Q2W and oral osimertinib Dose 1 QD until documentation of disease progression, intolerable toxicity, or development of other reason for treatment discontinuation, whichever occurs first. |
| Oleclumab Dose 1 + AZD4635 Dose 1 | EXPERIMENTAL | In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 1 QD. |
| Oleclumab Dose 1 + AZD4635 Dose 2 | EXPERIMENTAL | In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 1 Q2W and oral AZD4635 Dose 2 QD. |
| Oleclumab Dose 2 + AZD4635 Dose 2 | EXPERIMENTAL | In Part 1 (dose-escalation), participants will receive intravenous oleclumab Dose 2 Q2W and oral AZD4635 Dose 2 QD. |
| Dose-escalation: Oleclumab Dose 1 | EXPERIMENTAL | Participants will receive oleclumab Dose 1 intravenously (IV) every two weeks (Q2W) until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 2 | EXPERIMENTAL | Participants will receive oleclumab Dose 2 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 3 | EXPERIMENTAL | Participants will receive oleclumab Dose 3 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 4 | EXPERIMENTAL | Participants will receive oleclumab Dose 4 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1 | EXPERIMENTAL | Participants will receive oleclumab Dose 1 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1 | EXPERIMENTAL | Participants will receive oleclumab Dose 2 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1 | EXPERIMENTAL | Participants will receive oleclumab Dose 3 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1 | EXPERIMENTAL | Participants will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1 | EXPERIMENTAL | Participants with previously treated microsatellite stable-colorectal cancer (MSS-CRC) will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1 | EXPERIMENTAL | Participants with previously treated pancreatic adenocarcinoma will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1 | EXPERIMENTAL | Participants with previously treated EGFRm NSCLC will receive oleclumab Dose 4 IV followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Name | Type | Description |
|---|---|---|
| Oleclumab | DRUG | Oleclumab IV (intravenous infusion) |
| Durvalumab | DRUG | Durvalumab IV (intravenous infusion) |
| MEDI9447 (oleclumab) | DRUG | MEDI9447 administered intravenously |
| Gemcitabine | DRUG | Participants will receive IV infusion of gemcitabine as stated in arm description. |
| Nab-paclitaxel | DRUG | Participants will receive IV infusion of nab-paclitaxel as stated in arm description. |
| Oxaliplatin | DRUG | Participants will receive IV infusion of oxaliplatin as stated in arm description. |
| Folinic acid | DRUG | Participants will receive IV infusion of folinic acid as stated in arm description. |
| 5-FU | DRUG | Participants will receive IV infusion of 5-FU as stated in arm description. |
| Osimertinib | DRUG | Participants will receive osimertinib in combination with oleclumab as stated in the arms' description. |
| AZD4635 | DRUG | Participants will receive AZD4635 in combination with oleclumab as stated in the arms' description. |
INCLUSION CRITERIA: * Participant must be ≥ 18 years at the time of screening. * Histologically-documented NSCLC and have been treated with concurrent or sequential CRT for locally advanced, unresectable (Stage III) disease. * Documented tumour PD-L1 status by qualified lab (local or central). * Do...
MEDI9447 is an investigational monoclonal antibody being studied in advanced solid malignancies. It is being developed as an oncology therapy and has been evaluated in a Phase 1 clinical trial in Japanese patients with advanced solid tumors. It is not approved for any indication.
MEDI9447 is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company is responsible for the clinical development of this monoclonal antibody in oncology.
MEDI9447 is in Phase 1 clinical development. One Phase 1 trial has been completed, and no active trials are currently listed. The drug remains investigational and has not been approved for any indication.
MEDI9447 has been evaluated in a single Phase 1 trial, NCT03736473, titled A Phase I Study of MEDI9447 (Oleclumab) in Japanese Patients. The trial enrolled 6 participants with advanced solid malignancies in Japan and is now completed.
Yes, MEDI9447 is also known as oleclumab. The two names refer to the same monoclonal antibody. The Phase 1 trial NCT03736473 lists the drug as MEDI9447 (Oleclumab), confirming they are identical.