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

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02671435
• Collaborator: (none)
• Enrollment: 383
• Locations: 49
• Arms: 3
• Actual Duration (Months): 68.1
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of Durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in Adult Subjects 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 subjects with recurrent or metastatic colorectal cancer (CRC).

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Combination Product: Intervention	Phase 1/Phase 2

Detailed Description

The study consists of 3 parts: dose escalation (Part 1), dose expansion (Part 2), and dose exploration (Part 3). Part 1 will evaluate dose escalation of durvalumab in combination with monalizumab in adult subjects with select advanced solid tumor malignancies. Part 2 will evaluate further the identified dose of durvalumab in combination with monalizumab from Part 1 in adult subjects with select advanced solid tumor malignancies. Part 3 will evaluate dose exploration of durvalumab in combination with monalizumab and standard of care systemic therapy with or without biological agent, and monalizumab in combination with biological agent in adult subjects with CRC.

Study Design

• Study Type: Interventional
• Actual Enrollment: 383 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
• Actual Study Start Date: Feb 22, 2016
• Actual Primary Completion Date: Oct 26, 2021
• Actual Study Completion Date: Oct 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 -Dose escalation with 5 dose escalation cohorts Durvalumab and monalizumab	Combination Product: Intervention; Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab
Experimental: Part 2 - Dose expansion with 4 dose expansion cohorts Durvalumab with monalizumab	Combination Product: Intervention; Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab
Experimental: Part 3 -Dose Exploration with 10 dose exploration cohorts. Durvalumab and monalizumab and standard of standard of care systemic therapy with or without a biologic agent and monalizumab in combination with biologic agent in CRC.	Combination Product: Intervention; Biological: Durvalumab Biological: Monalizumab Biological: Cetuximab

Outcome Measures

Primary Outcome Measures

1. Occurrence of Drug Limited Toxicities (DLTs) [From Time of First dose through DLT Screening period]

   To assess by the occurrence of Drug Limited Toxicities (DLTs)

2. Number of patients with changes in vital signs from baseline [From time of screening through 90 days (+/- 7 days) after the last dose of study medication]

   To assess safety of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent or monalizumab + with biological agent

3. Occurrence of adverse events (AEs) [From time of screening through 90 days (+/- 7 days) after the last dose of study medication]

   To assess by the occurrence of adverse events (AEs)

4. Number of patients with changes in electrocariogram (ECG) from baseline [From time of screening through 90 days (+/- 7 days) after the last dose of study medication]

   To assess safety of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

5. Occurrence of serious adverse events (SAEs) [From time of screening through 90 days (+/- 7 days) after the last dose of study medication]

   To assess by the occurrence of serious adverse events (SAEs)

6. Number of patients with changes in laboratory parameters from baseline [From time of screening through 90 days (+/- 7 days) after the last dose of study medication]

   To assess safety of monalizumab +durva, or monalizumab +durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

7. Objective Response Rate (ORR) [From time of first dose of study medication through 5 years]

   To assess anti-tumor activity of monalizumab + durva without biological agent, or monalizumab + with biological agent

Secondary Outcome Measures

1. Expression of pre-treatment protein within the tumor microenvironment [From time of screening through 90 days (+/- 7 days) after the last dose of study medication]

   To assess biomarker predicting activity of monalizumab+durva in combo with standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

2. Number of subjects who develop anti-drug antibodies [From time of first dose through 90 days (+/- 7 days) after the last dose of study medication]

   To assess the immunogenicity of mona+durva with or without standard of care systemic therapy or biological agent, or monalizumab + with biological agent

3. Durva, monalizumab, biologic agent serum peak concentration (cMax) concentration for Pharmacokinetics [From time of first dose through 90 days (+/- 7 days) after the last dose of study medication]

   To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

4. Durva and monalizumab serum area under the concentration-time curve (AUC) concentration for Pharmacokinetics [From time of first dose through 90 days (+/- 7 days) after the last dose of study medication]

   To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, monalizumab + with biological agent

5. Durva and monalizumab serum clearance (CL) concentration for Pharmacokinetics [From time of first dose through 90 days (+/- 7 days) after the last dose of study medication]

   To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

6. Durva and monalizumab serum terminal elimination half-life (t1/2) concentration for Pharmacokinetics [From first dose through 90 days (+/- 7 days) after the last dose of study medication]

   To assess the pharmacokinetics of Durvalumab and monalizumab or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

7. Objective Response Rate (ORR) [From time of first dose of study medication through 5 years]

   To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

8. Progression Free Survival (PFS) [From time of first dose of study medication through 5 years]

   To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

9. Disease Control Rate (DC) [From time of first dose of study medication through 5 years]

   To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

10. Overall Survival (OS) [From time of first dose of study medication through 5 years]

    To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

11. Duration of Response (DoR) [From time of first dose of study medication through 5 years]

    To assess anti-tumor activity of monalizumab +durva, or monalizumab+durva +standard of care systemic therapy with or without biological agent, or monalizumab + with biological agent

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects must have histologic documentation of advanced recurrent or metastatic cancer.

2. Subjects must be at the recurrent/metastatic setting, with selected advanced solid tumors.

3. Subjects must have at least one lesion that is measurable by RECIST v1.1

4. Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have received more than two line of systemic therapy in the recurrent/metastatic setting.

Exclusion Criteria

1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.

2. Prior participation in clinical studies that include durvalumab alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed

3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment

4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35233
2	Research Site	Scottsdale	Arizona	United States	85258
3	Research Site	Duarte	California	United States	91010
4	Research Site	La Jolla	California	United States	92093
5	Research Site	Los Angeles	California	United States	90033
6	Research Site	Sacramento	California	United States	95817
7	Research Site	Santa Monica	California	United States	90404
8	Research Site	Aurora	Colorado	United States	80045
9	Research Site	Tampa	Florida	United States	33612
10	Research Site	Chicago	Illinois	United States	60611
11	Research Site	Baltimore	Maryland	United States	21231
12	Research Site	Boston	Massachusetts	United States	02215
13	Research Site	Detroit	Michigan	United States	48202
14	Research Site	New Brunswick	New Jersey	United States	08903
15	Research Site	Bronx	New York	United States	10461
16	Research Site	Lake Success	New York	United States	11042
17	Research Site	New York	New York	United States	10065
18	Research Site	Providence	Rhode Island	United States	02903
19	Research Site	Nashville	Tennessee	United States	37203
20	Research Site	Dallas	Texas	United States	75235
21	Research Site	San Antonio	Texas	United States	78229
22	Research Site	Salt Lake City	Utah	United States	84112
23	Research Site	Blacktown		Australia	2148
24	Research Site	Clayton		Australia	3168
25	Research Site	Waratah		Australia	2298
26	Research Site	Bruxelles		Belgium	1200
27	Research Site	Edegem		Belgium	2650
28	Research Site	Leuven		Belgium	3000
29	Research Site	Vancouver	British Columbia	Canada	V5Z 4E6
30	Research Site	Toronto	Ontario	Canada	M5G 1Z5
31	Research Site	Marseille CEDEX 5		France	13385
32	Research Site	Nantes CEDEX 1		France	44093
33	Research Site	Debrecen		Hungary	4032
34	Research Site	Milano		Italy	20132
35	Research Site	Milano		Italy	20141
36	Research Site	Seoul		Korea, Republic of	03080
37	Research Site	Seoul		Korea, Republic of	03722
38	Research Site	Seoul		Korea, Republic of	05505
39	Research Site	Seoul		Korea, Republic of	06351
40	Research Site	Seoul		Korea, Republic of	06591
41	Research Site	Grafton		New Zealand	1023
42	Research Site	Barcelona		Spain	08035
43	Research Site	Madrid		Spain	28027
44	Research Site	Madrid		Spain	28034
45	Research Site	Málaga		Spain	29010
46	Research Site	Pamplona		Spain	31008
47	Research Site	Sevilla		Spain	41013
48	Research Site	London		United Kingdom	SW2 6JJ
49	Research Site	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• MedImmune LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02671435
• Other Study ID Numbers: D419NC00001; D419NC00001
• First Posted: Feb 2, 2016
• Last Update Posted: Jan 19, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by MedImmune LLC: Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
• Additional relevant MeSH terms: Neoplasms

Study Results

No Results Posted as of Jan 19, 2022