A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors

Condition(s) studied

Investigational drug(s) / intervention(s)

Monalizumab: Participants will receive IV infusion of monalizumab as stated in arm description.

Durvalumab: Participants will receive IV infusion of durvalumab as stated in arm description.

Cetuximab: Participants will receive IV infusion of cetuximab as stated in arm description.

mFOLFOX6: Participants will receive IV infusion of mFOLFOX as stated in arm description.

Bevacizumab: Participants will receive IV infusion of bevacizumab as stated in arm description.

Study summary

This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, pharmacokinetic (PK), pharmacodynamics, and immunogenicity of durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in adult participants with selected advanced solid tumors and the combination of durvalumab and monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and monalizumab (IPH2201) with biological agent administered to participants with recurrent or metastatic colorectal cancer (CRC).

Eligibility

Primary outcome measure(s)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) — Day 1 through 246.9 weeks (maximum observed duration)
  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. Any TEAEs data is inclusive of both serious and other adverse events (non-serious).
• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Change from baseline in SBP and DBP (minimum post baseline change \[PBC\] and maximum PBC) are reported.
• Change From Baseline in Respiratory Rate (RR) — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Change from baseline in RR (minimum PBC and maximum PBC) are reported.
• Change From Baseline in Pulse Rate (PR) — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Change from baseline in PR (minimum PBC and maximum PBC) are reported.
• Change From Baseline in Body Temperature (BT) — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Change from baseline in BT (minimum PBC and maximum PBC) are reported.
• Change From Baseline in Oxygen Saturation (OS) — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Change from baseline in OS (minimum PBC and maximum PBC) are reported.
• Number of Participants With Notable Change in QTcF and QTcB From Baseline — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Participants who had notable QTcF and QTcB interval change from baseline are reported.
• Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters — Day 1 (baseline) through 246.9 weeks (maximum observed duration)
  Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported.
• Number of Participants With Dose Limiting Toxicities (DLTs) — From Day 1 to 28 days after the first dose of study drugs
  DLT: Any study drug related Grade (G) 3 or higher toxicity that occurred during DLT evaluation period including: any G\>=3 noninfectious colitis/pneumonitis, liver transaminase elevation (TE) \>=5 but =\<8 upper limit of normal (ULN), any G4 immune-mediated AE (imAE)/immune-related AE (irAE), any G\>=3 clinically significant non-hematologic toxicity, TE \>8 ULN or total bilirubin (TBL) \>5 ULN, increase in AST or ALT \>=3 ULN along with TBL \>=2 ULN, thrombocytopenia (G3/4 associated with G3/higher hemorrhage, G3 that did not improve by at least 1 grade within 7 days, and G4), G4 febrile neutropenia (FN), G3 FN of \>=5 days and G3 FN regardless of duration, G4 neutropenia of \>7 days, G3/4 neutropenia not associated with fever/systemic infection, and anemia (G3 and G4).
• Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B — Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
  The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST V 1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between.

Trial sites (49)

+ 9 more sites — see the full list on the official registry below.

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