MesotheliomaPhase 2NCT03075527
A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma
A Phase 2 study testing Tremelimumab and Durvalumab in people with Mesothelioma, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is studying a pair of immunotherapies as a possible treatment for malignant pleural mesothelioma. The drugs involved in this study are: Durvalumab Tremelimumab Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma
- What is being tested?
- Tremelimumab and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2017to 16 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained prior to any study-specific procedures not considered part of routine medical care
- Histologically or cytologically confirmed unresectable or medically inoperable malignant pleural mesothelioma
- Disease progression after treatment with at least one line of chemotherapy that included a first-line platinum agent in combination with an anti-folate
- Participants must have measurable disease according to modified RECIST for pleural malignant mesothelioma. (Bone metastases are not considered measurable.) Prior radiation to the only site of measurable disease will make the participant ineligible unless the lesion has been demonstrated to grow after completion of radiation therapy.
- Participants must be willing and able to undergo a biopsy at the start of this study and an on-treatment biopsy if safe and feasible.
- Participants must have be at least 28 days from any major surgery.
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- ECOG performance status of 0 or 1.
- Subjects must have adequate hematologic, renal, and organ and marrow function
- Age 18 years or older
- Female subjects of childbearing potential who are sexually active with a non sterilized male partner must agree to use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of investigational product. Male partners of a female subject must also agree to use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female patients should refrain from breastfeeding throughout this period.
- Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal (defined as greater than or equal to 12 months with no menses without an alternative medical cause)
- Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use male condom plus spermicide from screening through 180 days after the last dose of investigational product. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male patients should refrain from sperm donation throughout this period. Female partners of a male subject must use a highly effective method of contraception throughout this period.
- Ability to understand and the willingness to sign a written informed consent document
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
Who cannot join
- Previous treatment with an immune check-point inhibitors, CTLA-4, PD-1, or PD-L1, including prior treatment with either durvalumab or tremelimumab
- Known central nervous system metastasis. Patients with known brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease may be enrolled if they have been treated, are no longer taking corticosteroids, and have been stable on imaging for at least 3 weeks
- Subjects currently receiving systemic corticosteroids above 10 mg per day for more than 14 days; subjects receiving other systemic immunosuppressive drugs for more than 14 days. Exceptions include: inhaled, intranasal, ophthalmic, and topical corticosteroids, local corticosteroid injections (e.g., intra-articular injections), and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan premedication)
- Subjects with medical conditions that require the chronic use of systemic corticosteroids. Exceptions include: inhaled, intranasal, ophthalmic, and topical corticosteroids, local corticosteroid injections (e.g., intra-articular injections), and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan premedication)
- Active or prior documented autoimmune disease within the past 2 years, including but not limited to systemic lupus erythematosus, sarcoidosis syndrome, or Wegener's granulomatosis. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, celiac disease, diverticulitis), or any other chronic, serious gastrointestinal condition associated with diarrhea. NOTE: Subjects with known diverticulosis are permitted to enroll.
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- History of interstitial lung disease or pneumonitis that has required steroid administration.
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to tremelimumab, durvalumab, or any excipient
- Known history of active tuberculosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
- Participants with a history of a second primary malignancy. Exceptions include: patients with a history of malignancies that were treated curatively and have not recurred within 5 years prior to study entry; resected basal and squamous cell carcinomas of the skin, and completely resected carcinoma in situ of any type.
- Participants who have had chemotherapy, biologic therapy, or investigational therapy within 21 days (including bevacizumab) or radiotherapy within 7 days prior to entering the study or those who have not recovered from adverse events due to agents administered
- Any history of a prior immune-related adverse event (irAE) at least or greater than grade 3 while receiving any previous immunotherapy agent.
- Participants who are receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Gastritis
- Symptomatic congestive heart failure
- Severe hypertension (defined as BP at least or greater than160/100 during the screening period despite optimal medical management)
- Unstable angina pectoris
- Cardiac arrhythmia
- Active bleeding diatheses
- Active peptic ulcer disease
- Psychiatric illness/social situations that would limit compliance with study requirements
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
- Known past or present medical history HIV-positive
- Subjects with known acute or chronic hepatitis B or hepatitis C.
- Pregnant women are excluded from this study because tremelimumab and durvalumab have unknown effects on the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tremelimumab or durvalumab, breastfeeding women are also excluded. Female subjects of child bearing potential must have a negative serum pregnancy test obtained prior to trial registration.
- Subjects who are involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Subjects who have undergone a pneumonectomy due to known potential for pulmonary toxicities and heightened risk for complications.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
This research study is studying a pair of immunotherapies as a possible treatment for malignant pleural mesothelioma.
The drugs involved in this study are:
- Durvalumab
- Tremelimumab
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved durvalumab or tremelimumab as a treatment for any disease.
In this research study, the investigators are studying if the study drug can help your cancer compared to the usual approach to treating malignant pleural mesothelioma . Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells. Tremelimumab blocks a receptor on immune cells that normally suppresses immune attack. These two study drugs have been used alone for mesothelioma but the combination has not yet been tested for mesothelioma. These two drugs have been used for cancers such as melanoma and have been effective than using either drug alone.
- Conditions
- Mesothelioma
- Being tested
- Tremelimumab, Durvalumab
- Keywords
- Mesothelioma
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TremelimumabDrug
Also called CP-675,206
Tremelimumab blocks a receptor on immune cells that normally suppresses immune attack.
DurvalumabDrug
Also called MEDI-4736
Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells.
| Study group | Role | What they receive |
|---|---|---|
| Tremelimumab + Durvalumab | Experimental | Subjects will receive durvalumab and tremelimumab both via intravenous infusion once per day for every 28 day cycles (+ 7 days). Participants will receive tremelimumab for up to 4 cycles (4 doses). Beginning with cycle 5 day 1, subjects will continue to receive durvalumab alone, until clinical or radiological progression. Receives: Drug: Tremelimumab; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment based on RECIST v1.1 criteria.
Measured: ORR was assessed every 8 weeks from Cycle 1 Day 1 until date of documented disease progression or death. The median treatment duration is 1.91 months with range (0.00 months - 23.46 months).
Secondary outcomes (4)
Median Overall Survival (OS)
OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Measured: OS is assessed from date of registration until date of death on-treatment or during follow-up. Survival data collection in long-term follow-up every 3-4 months. Median follow-up for survival is of 27.33 months with range (0.76 months - 50.40 months).
Median Progression Free Survival (PFS)
PFS based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) defined per RECIST 1.1 criteria. or death, or is censored at time of last disease assessment.
Measured: Participants were evaluated for response every 8 weeks on study and in long-term survival followed-up every 3-4 months. Median follow-up for survival is of 27.33 months with range (0.76 months - 50.40 months).
Median Duration of Response (DOR)
DOR is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (or censored at the date of last disease evaluation).
Measured: The median of treatment duration is 1.91 months with range (0.00 months - 23.46 months).
Grade 4-5 Treatment-related Toxicity Rate
All grade 4-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4.03 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.
Measured: Toxicity is assessed from the time of first dose of study medication until the participant comes off study. The median of treatment duration is 1.91 months with range (0.00 months - 23.46 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2017
- Study start10 Apr 2017
- Primary completion7 Jun 2019
- Study completion16 Dec 2024
Why it stopped: Criteria not met for second stage at time of interim analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Biagio Ricciuti, Dana-Farber Cancer Institute
- Investigators
- Mark M. Awad, MD, PhD, Principal investigator, Dana-Farber Cancer InstituteBiagio Ricciuti, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03075527
- Sponsor's protocol ID
- 16-549
- Status last verified
- Dec 2025
- First submitted
- 2 Mar 2017
- Last updated
- 16 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Durvalumab in Combination With Tremelimumab in Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT03075527
- Acronym / sponsor ID
- 16-549
- Conditions
- Mesothelioma
- Keywords
- Mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Criteria not met for second stage at time of interim analysis
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 10 Apr 2017 (actual)
- Primary completion
- 7 Jun 2019 (actual)
- Study completion
- 16 Dec 2024 (actual)
- First posted
- 9 Mar 2017 (actual)
- Results
- Posted 12 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a pair of immunotherapies as a possible treatment for malignant pleural mesothelioma.
The drugs involved in this study are:
- Durvalumab
- Tremelimumab
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved durvalumab or tremelimumab as a treatment for any disease.
In this research study, the investigators are studying if the study drug can help your cancer compared to the usual approach to treating malignant pleural mesothelioma . Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells. Tremelimumab blocks a receptor on immune cells that normally suppresses immune attack. These two study drugs have been used alone for mesothelioma but the combination has not yet been tested for mesothelioma. These two drugs have been used for cancers such as melanoma and have been effective than using either drug alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tremelimumab + Durvalumab | Experimental | Drug: Tremelimumab, Drug: DurvalumabSubjects will receive durvalumab and tremelimumab both via intravenous infusion once per day for every 28 day cycles (+ 7 days). Participants will receive tremelimumab for up to 4 cycles (4 doses). Beginning with cycle 5 day 1, subjects will continue to receive durvalumab alone, until clinical or radiological progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Written informed consent obtained prior to any study-specific procedures not considered part of routine medical care
- Histologically or cytologically confirmed unresectable or medically inoperable malignant pleural mesothelioma
- Disease progression after treatment with at least one line of chemotherapy that included a first-line platinum agent in combination with an anti-folate
- Participants must have measurable disease according to modified RECIST for pleural malignant mesothelioma. (Bone metastases are not considered measurable.) Prior radiation to the only site of measurable disease will make the participant ineligible unless the lesion has been demonstrated to grow after completion of radiation therapy.
- Participants must be willing and able to undergo a biopsy at the start of this study and an on-treatment biopsy if safe and feasible.
Key exclusion criteria (32 listed)
- Previous treatment with an immune check-point inhibitors, CTLA-4, PD-1, or PD-L1, including prior treatment with either durvalumab or tremelimumab
- Known central nervous system metastasis. Patients with known brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease may be enrolled if they have been treated, are no longer taking corticosteroids, and have been stable on imaging for at least 3 weeks
- Subjects currently receiving systemic corticosteroids above 10 mg per day for more than 14 days; subjects receiving other systemic immunosuppressive drugs for more than 14 days. Exceptions include: inhaled, intranasal, ophthalmic, and topical corticosteroids, local corticosteroid injections (e.g., intra-articular injections), and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan premedication)
- Subjects with medical conditions that require the chronic use of systemic corticosteroids. Exceptions include: inhaled, intranasal, ophthalmic, and topical corticosteroids, local corticosteroid injections (e.g., intra-articular injections), and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan premedication)
- Active or prior documented autoimmune disease within the past 2 years, including but not limited to systemic lupus erythematosus, sarcoidosis syndrome, or Wegener's granulomatosis. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TremelimumabAlso: CP-675,206Tremelimumab blocks a receptor on immune cells that normally suppresses immune attack. | Drug | Tremelimumab + Durvalumab |
| DurvalumabAlso: MEDI-4736Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells. | Drug | Tremelimumab + Durvalumab |
Primary outcome
Overall Response Rate (ORR)
Time frame: ORR was assessed every 8 weeks from Cycle 1 Day 1 until date of documented disease progression or death. The median treatment duration is 1.91 months with range (0.00 months - 23.46 months).
Overall Response Rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment based on RECIST v1.1 criteria.
4 secondary outcomes
Median Overall Survival (OS)
Time frame: OS is assessed from date of registration until date of death on-treatment or during follow-up. Survival data collection in long-term follow-up every 3-4 months. Median follow-up for survival is of 27.33 months with range (0.76 months - 50.40 months).
Median Progression Free Survival (PFS)
Time frame: Participants were evaluated for response every 8 weeks on study and in long-term survival followed-up every 3-4 months. Median follow-up for survival is of 27.33 months with range (0.76 months - 50.40 months).
Median Duration of Response (DOR)
Time frame: The median of treatment duration is 1.91 months with range (0.00 months - 23.46 months).
Grade 4-5 Treatment-related Toxicity Rate
Time frame: Toxicity is assessed from the time of first dose of study medication until the participant comes off study. The median of treatment duration is 1.91 months with range (0.00 months - 23.46 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark M. Awad, MD, PhD principal investigator
Dana-Farber Cancer Institute
Biagio Ricciuti, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tremelimumab and Durvalumab in people with Mesothelioma, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: ORR was assessed every 8 weeks from Cycle 1 Day 1 until date of documented disease progression or death. The median treatment duration is 1.91 months with range (0.00 months - 23.46 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.