Phase 2
Completed N=27
A Phase 1/2 Study to Evaluate MEDI4736
Source: ClinicalTrials.gov NCT01693562 ↗Enrolled (actual)
27
Serious AEs
54.5%
Results posted
May 2021
Primary outcomePrimary: Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase — 0; 0; 0; 0 Participants
Summary
This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
3; 4; 3; 3; 7; 21 | — |
| PRIMARY Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
0; 3; 0; 1; 3; 2 | — |
| PRIMARY Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
1; 0; 0; 4; 1; 0 | — |
| PRIMARY Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC Who Had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase |
10.3 | — |
| PRIMARY ORR Assessed by BICR in Participants With Squamous NSCLC Who Had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase |
12.8; 12.9 | — |
| PRIMARY ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) Who Had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase |
27.6 | — |
| SECONDARY Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase |
5.144; 25.063; 130.546; 399.863; 1780.152; 2943.770 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase |
2.780; 7.969; 22.773; 70.807; 293.540; 427.085 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase. |
4; 1; 0; 6; 0; 0 | — |
| SECONDARY Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase |
0; 3; 4; 39; 10; 80 | — |
| SECONDARY Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
1; 1; 1; 5; 0; 1 | — |
| SECONDARY Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase |
12.37; 17.74 | — |
| SECONDARY DoR Assessed by Investigator in the Dose-expansion Phase |
19.71; 14.75; 9.95; 16.20; NA; 9.23 | — |
| SECONDARY Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase |
25.5; 44.4 | — |
| SECONDARY DCR Assessed by Investigator in the Dose-expansion Phase |
33.9; 45.5; 51.7; 65.0; 57.1; 37.5 | — |
| SECONDARY Progression-free Survival (PFS) Assessed by BICR in NSCLC Cohort in the Dose-expansion Phase |
2.1 | — |
| SECONDARY PFS Assessed by BICR in SCCHN Cohort in the Dose-expansion Phase |
1.4 | — |
| SECONDARY PFS Assessed by Investigator in the Dose-expansion Phase |
1.4; 1.5; 2.6; 2.7; 2.8; 1.4 | — |
| SECONDARY OS in the Dose-Expansion Phase |
8.4; 11.6; 12.4; 13.2; NA; 8.4 | — |
| SECONDARY ORR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
5.9; 17.6; 27.7 | — |
| SECONDARY ORR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
7.0; 20.9; 33.3 | — |
| SECONDARY DoR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
12.25; NA; NA | — |
| SECONDARY DoR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
14.82; 19.71; NA | — |
| SECONDARY DCR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
21.2; 35.2; 43.6 | — |
| SECONDARY DCR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
30.2; 43.3; 53.9 | — |
| SECONDARY PFS Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
1.4; 1.5; 1.9 | — |
| SECONDARY PFS Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
1.4; 1.8; 2.8 | — |
| SECONDARY OS in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
4.8; 10.5; 19.8 | — |
| SECONDARY Adjusted Comparison of PFS by PD-L1 Status in UC Cohort in the Dose-expansion Phase |
2.6; 1.5 | 0.016 sig |
| SECONDARY Adjusted Comparison of OS by PD-L1 Status in UC Cohort in the Dose-expansion Phase |
18.4; 3.4 | 0.0046 sig |
Eligibility Criteria
Inclusion Criteria
- Age 18 or older.
- In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
- In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, participants must have failed, be intolerant to, be ineligible for, or have refused
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
- Adequate organ and marrow function.
- Participants must have at least 1 measurable lesion.
- Available archived tumor tissue sample.
- Willingness to provide consent for biopsy sample (dose-expansion only)
Exclusion Criteria
- Any prior Grade ≥ 3 immune-mediated adverse event (imAE) while receiving immunotherapy
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors.
- Active or prior documented autoimmune disease within the past 2 years
- History of primary immunodeficiency
- History of organ transplant that requires use of immunosuppressives
- Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment
- Other invasive malignancy within 2 years
- Women who are pregnant or lactating
- Uncontrolled intercurrent illness
- Known history of tuberculosis
- Known to be human immunodeficiency virus (HIV) positive
- Known to be Hepatitis B or C positive (except HCC participants)
Data sourced from ClinicalTrials.gov (NCT01693562). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.