Renal Clear Cell CarcinomaPhase 2CALYPSONCT02819596
MEDI4736 Combinations in Metastatic Renal Cell Carcinoma
A Phase 2 study testing Savolitinib, MEDI4736 and Tremelimumab in people with Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma, run by Queen Mary University of London at 1 site in United Kingdom.
Trial summary
This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer. The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Clear Cell Carcinoma, Renal Papillary Cell Carcinoma
- What is being tested?
- Savolitinib, MEDI4736 and Tremelimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 May 2016to 17 Jul 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 prior to performing any protocol-related procedures, including study specific screening procedures.
- Age ≥ 18 years at the time of registration/enrolment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥12 weeks
- Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (stage IV) renal cell cancer with a component of either clear cell cancer or papillary cancer. Patients with a component of both must be enrolled into the cohort with the predominant tumour type.
- Clear cell renal cancer patients must have experienced progressive disease after exposure to Vascular Endothelial growth rate (VEGF) targeted therapy.
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- Sarcomatoid cell renal cancer patients must have experienced progressive disease after exposure to VEGF targeted therapy.
- Papillary cell renal cancer patients must be considered to be VEGF treatment naive or treatment refractory to be eligible.
- Evidence of measurable disease as per RECIST v1.1 (i.e., ≥1 malignant tumour mass that can be accurately measured in at least 1 dimension ≥ 20 mm with conventional computerized tomography CT Scan or Magnetic Resonance Imaging (MRI), or ≥10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable.
- Adequate normal organ, marrow and coagulation function as defined by the following criteria:
- Representative formalin-fixed paraffin-embedded (FFPE) tumour block with an associated anonymised pathology report must be available for central testing and determined to be evaluable for tumour assessment of PD-L1 and Met. PD-L1 and Met related testing will be required prior to study entry only for the biomarker enrichment phase of the trial. (every effort should be made to obtain FFPE blocks however unstained fresh tissue slides and core needle biopsies will suffice).
- Patients with known tumour thrombus or deep vein thrombosis (DVT) are eligible if stable on low molecular weight heparin (LMWH) for ≥ 4 weeks.
- Negative serum or urine pregnancy test within 2 weeks prior to the first dose of IMP (for female patients of childbearing potential only).
- Agreement to use adequate contraceptive measures (Section 6.18).
- Ability to swallow and retain oral medications.
- Willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow up.
Who cannot join
- Participation in another clinical study with an investigational product within 28 days prior to enrolment in the study.
- Any previous treatment with an anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody (including MEDI4736), CD137 agonists, c-MET inhibitors or pathway-targeting agents, or CTLA-4. Patients with limited c-MET inhibitor exposure must be discussed with the study medical monitor.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) within 2 weeks or five half-lives of the anti-cancer therapy prior to the first dose of study drug, or radical radiotherapy within 4 weeks prior to the first dose of study drug.
- Patients receiving strong inducers of CYP3A4, strong inhibitors of CYP3A4 or CYP1A2 or CYP3A4 substrates which have a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort) are excluded from enrolment in the study (see Appendix I).
- Currently receiving treatment with therapeutic doses of warfarin sodium. LMWH is allowed.
- Current or prior use of immunosuppressive medication within 21 days before the first dose of MEDI4736 or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
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- Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL] -2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736 or tremelimumab or anticipation that such a live, attenuated vaccine will be required during the study.
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
- History of another primary malignancy other than renal cell carcinoma within 3 years prior to Cycle 1, Day 1 with the exception of:
- Malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of study drug and of low potential risk for recurrence.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease e.g. cervical cancer in situ or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA <10ng/mL undergoing active surveillance and treatment naive). Patients on surveillance for low risk prostate cancer are also eligible - please discuss with medical monitor.
- Mean resting QT interval corrected for heart rate (QTc) >470ms for women and >450ms for men calculated from triplicate electrocardiograms (ECGs) using Fridericia's correction.
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
- Any unresolved toxicity of CTCAE grade >2 from previous anti-cancer therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the IMP may be included e.g. hearing loss, peripheral neuropathy etc.
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
- Active or prior documented autoimmune disease within the past 2 years including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible for this study.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or history of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- History of primary immunodeficiency
- History of allogeneic prior allogeneic stem cell or solid organ transplant
- History of hypersensitivity to MEDI4736, tremelimumab, or any excipient or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- History of hypersensitivity to savolitinib and its excipients.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (SBP>160mmHg or Diastolic blood pressure >100mmHg, patients with values above these levels must have their blood pressure controlled with medication prior to starting treatment), unstable angina pectoris, cardiac arrhythmia, or any factors that increase the risk of QTc prolongation, any clinically important abnormalities in rhythm, conduction or morphology of resting ECGs, active peptic ulcer disease or gastritis, Type I diabetes mellitus, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, Patients with a known left ventricular ejection fraction (LVEF) < 40% will be excluded.
- Major surgical procedure within 4 weeks prior to enrolment, minor surgical procedure within 7 days of enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
- Active tuberculosis or known history of previous clinical diagnosis of tuberculosis.
- History of leptomeningeal carcinomatosis
- Female subjects who are pregnant or breast-feeding
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Trial locations and contacts
1 site in 1 country.
About this study
This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer.
The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. MEDI4736 and tremelimumab work with the immune system to help the body fight against tumour cells with immune cells. Savolitinib works to correct a faulty signal which causes tumour growth.
Read more
If a patient is eligible for the study and decides to take part, they will be enrolled into one of 3 stages of the study.
- First stage [CLOSED TO RECRUITMENT]: aims to find the optimal dose of MEDI4736+savolitinib.
- Second stage [CLOSED TO RECRUITMENT]: patients with papillary cell cancer will be treated with MEDI4736+savolitinib. Patients with clear cell cancer will be randomised to one of four treatment arms and receive MEDI4736, savolitinib, MEDI4736+savolitinib, or MEDI4736+tremelimumab.
- Third stage [NOT YET OPEN TO RECRUITMENT]: patients will be tested for biomarkers before enrolment, and depending on the results will be allocated to one of 2 treatments (MEDI4736 alone or MEDI4736+tremelimumab) to see if certain biomarkers are linked to drug efficacy.
Read the detailed description
This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer.
The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. MEDI4736 and tremelimumab work with the immune system to help the body fight against tumour cells with immune cells. Savolitinib works to correct a faulty signal which causes tumour growth.
- Being tested
- Savolitinib, MEDI4736, Tremelimumab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SavolitinibDrug
Also called Volitinib, AZD6094
MEDI4736Drug
Also called Durvalumab
TremelimumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Savolitinib | Experimental | 600 mg of Savolitinib monotherapy will administered once a day until study completion or withdrawal Receives: Drug: Savolitinib |
| MEDI4736 | Experimental | 1500 mg MEDI4736 will be administered every 4 weeks until study completion or withdrawal Receives: Drug: MEDI4736 |
| Savolitinib and MEDI4736 | Experimental | Savolitinib and MEDI4736 will be administered at the Recommended Phase 2 dose ascertained in the phase Ib. Receives: Drug: Savolitinib; Drug: MEDI4736 |
| Tremelimumab and MEDI4736 | Experimental | Subjects will receive 75 mg of Tremelimumab and 1500 mg medi4736 every 4 weeks for the first four cycles, then 750 mg MEDI4736 every 4 weeks until study completion or withdrawal. Receives: Drug: MEDI4736; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify Dose Limiting Toxicity -Phase Ib
The endpoint of this objective is to identify Dose-Limiting Toxicity that occurs during the DLT assessment phase and is almost certainty/probably dose related and drug related .Toxicity that is clearly and directly related to the primary disease or another aetiology is excluded from this definition.
Measured: 6 months
Overall response (OR) in patients with metastatic clear cell renal cancer
Overall response rate based on RECIST V1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
Measured: 18 months
Overall response (OR) in patients with metastatic Papillary cell renal cancer
Overall response rate based on RECIST V1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
Measured: 18 months
Overall response (OR)in patients with metastatic renal cell cancer -Biomarker enrichment phase
Overall response rate based on RECIST v1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
Measured: 11 months
Secondary outcomes (12)
De-escalation phase - PK-Cmax measurement
Measurement of Cmax for MEDI4736 and savolitinib
Measured: 14 months
De-escalation phase - PK-Tmax measurement
Measurement of tmax for MEDI4736 and savolitinib
Measured: 14 months
De-escalation phase -PK AUC (0-t) measurement
Measurement of AUC(0-t)for MEDI4736 and savolitinib
Measured: 14 months
De-escalation phase - PK AUCs measurement
Measurement of AUCs for MEDI4736 and savolitinib
Measured: 14 months
De-escalation phase -PK Css measurement
Measurement of Css max for MEDI4736 and savolitinib
Measured: 14 months
De-escalation phase -PK Css min measurement
Measurement of Css min. for MEDI4736 and savolitinib
Measured: 14 months
Expansion Phase (IIa) -Identify Progression free survival (PFS)
PFS defined as the time from the date of randomisation/enrolment to the date of first documented tumour progression (RECIST V1.1) or death from any cause , whichever occurs first
Measured: 18 months
Expansion Phase (IIa) -Identify overall Survival (OS)
OS defined as the time from study entry to death from any cause. All deaths will be included whether they occur on study or following treatment discontinuation. For patients who have not died, overall survival will be censored at the date of last contact
Measured: 18 months
Expansion Phase (IIa) -Identify duration of response
Duration of response defined as the time from first documentation of CR or PR to disease progression (RECIST v1.1) or death from any cause, whichever occurs first.
Measured: 18 months
Biomarker positive patient analysis
Patients that have test positive for C-met or PD-L1 alterations;OS defined as the time from study entry to death from any cause.All deaths will be included whether they occur on study or following treatment discontinuation. For patients who have not died, overall survival will be censored at the date of last contact
Measured: 11 months
Biomarker positive patient analysis
Patients that have test positive for C-met or PD-L1 alterations; PFS defined as the time from the date of registration to the date of the first documented tumour progression as per RECIST V1.1 or death from any cause , whichever occurs first
Measured: 11 months
Expansion Phase (IIa) -Best Response
Best response after 24 weeks of treatment as assessed by RECIST v1.1.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start3 May 2016
- Primary completion17 Jul 2024
- Study completion17 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Renal Clear Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Vall d'Hebron Institute of Oncology, AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02819596
- Sponsor's protocol ID
- 010580QM
- Acronym
- CALYPSO
- Status last verified
- Nov 2024
- First submitted
- 22 Feb 2016
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Powles T et al. CALYPSO: A three-arm randomized phase II study of durvalumab alone or with savolitinib or tremelimumab in previously treated advanced clear cell renal cancer. Journal of Clinical Oncology 40, no. 17_suppl (June 10, 2022) LBA4503-LBA4503
Suarez C, Larkin JMG, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite F, Ralph C, Srinivasan G, Mendez-Vidal MJ, Hartmaier R, Markovets A, Prendergast A, Szabados B, Mousa K, Powles T. Phase II Study Investigating the Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer (CALYPSO). J Clin Oncol. 2023 May 10;41(14):2493-2502. doi: 10.1200/JCO.22.01414. Epub 2023 Feb 21.
PubMed 36809050Suarez Rodriguez et al. Overall survival results for durvalumab and savolitinib in metastatic papillary renal cancer. Journal of Clinical Oncology 2020 38:6_suppl, 619-619.
Suarez Rodriguez et al Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer. J Clin Oncol 39, 2021 (suppl 15; abstr 4511).
Jackson-Spence F, Larkin J, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite FC, Ralph C, Srinivasan G, Mendez-Vidal MJ, Childress M, Li W, Boyle P, Gasco A, Markovets A, Hartmaier R, Ackerman C, Szabados BE, Priyadarshini G, Jamal F, Powles T, Suarez C. CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer. J Clin Oncol. 2026 Apr 20;44(12):1076-1082. doi: 10.1200/JCO-25-01840. Epub 2026 Mar 20.
PubMed 41861260
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MEDI4736 Combinations in Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02819596
- Acronym / sponsor ID
- CALYPSO / 010580QM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Vall d'Hebron Institute of Oncology, AstraZeneca
- Study start
- 3 May 2016 (actual)
- Primary completion
- 17 Jul 2024 (actual)
- Study completion
- 17 Jul 2024 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer.
The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. MEDI4736 and tremelimumab work with the immune system to help the body fight against tumour cells with immune cells. Savolitinib works to correct a faulty signal which causes tumour growth.
If a patient is eligible for the study and decides to take part, they will be enrolled into one of 3 stages of the study.
- First stage [CLOSED TO RECRUITMENT]: aims to find the optimal dose of MEDI4736+savolitinib.
- Second stage [CLOSED TO RECRUITMENT]: patients with papillary cell cancer will be treated with MEDI4736+savolitinib. Patients with clear cell cancer will be randomised to one of four treatment arms and receive MEDI4736, savolitinib, MEDI4736+savolitinib, or MEDI4736+tremelimumab.
- Third stage [NOT YET OPEN TO RECRUITMENT]: patients will be tested for biomarkers before enrolment, and depending on the results will be allocated to one of 2 treatments (MEDI4736 alone or MEDI4736+tremelimumab) to see if certain biomarkers are linked to drug efficacy.
Detailed description
This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer.
The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. MEDI4736 and tremelimumab work with the immune system to help the body fight against tumour cells with immune cells. Savolitinib works to correct a faulty signal which causes tumour growth.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Savolitinib | Experimental | Drug: Savolitinib600 mg of Savolitinib monotherapy will administered once a day until study completion or withdrawal |
| MEDI4736 | Experimental | Drug: MEDI47361500 mg MEDI4736 will be administered every 4 weeks until study completion or withdrawal |
| Savolitinib and MEDI4736 | Experimental | Drug: Savolitinib, Drug: MEDI4736Savolitinib and MEDI4736 will be administered at the Recommended Phase 2 dose ascertained in the phase Ib. |
| Tremelimumab and MEDI4736 | Experimental | Drug: MEDI4736, Drug: TremelimumabSubjects will receive 75 mg of Tremelimumab and 1500 mg medi4736 every 4 weeks for the first four cycles, then 750 mg MEDI4736 every 4 weeks until study completion or withdrawal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent prior to performing any protocol-related procedures, including study specific screening procedures.
- Age ≥ 18 years at the time of registration/enrolment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥12 weeks
- Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (stage IV) renal cell cancer with a component of either clear cell cancer or papillary cancer. Patients with a component of both must be enrolled into the cohort with the predominant tumour type.
Key exclusion criteria (31 listed)
- Participation in another clinical study with an investigational product within 28 days prior to enrolment in the study.
- Any previous treatment with an anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody (including MEDI4736), CD137 agonists, c-MET inhibitors or pathway-targeting agents, or CTLA-4. Patients with limited c-MET inhibitor exposure must be discussed with the study medical monitor.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) within 2 weeks or five half-lives of the anti-cancer therapy prior to the first dose of study drug, or radical radiotherapy within 4 weeks prior to the first dose of study drug.
- Patients receiving strong inducers of CYP3A4, strong inhibitors of CYP3A4 or CYP1A2 or CYP3A4 substrates which have a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort) are excluded from enrolment in the study (see Appendix I).
- Currently receiving treatment with therapeutic doses of warfarin sodium. LMWH is allowed.
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 |
|---|---|---|
| SavolitinibAlso: Volitinib, AZD6094 | Drug | Savolitinib, Savolitinib and MEDI4736 |
| MEDI4736Also: Durvalumab | Drug | MEDI4736, Savolitinib and MEDI4736, Tremelimumab and MEDI4736 |
| Tremelimumab | Drug | Tremelimumab and MEDI4736 |
Primary outcome
Identify Dose Limiting Toxicity -Phase Ib
Time frame: 6 months
The endpoint of this objective is to identify Dose-Limiting Toxicity that occurs during the DLT assessment phase and is almost certainty/probably dose related and drug related .Toxicity that is clearly and directly related to the primary disease or another aetiology is excluded from this definition.
Overall response (OR) in patients with metastatic clear cell renal cancer
Time frame: 18 months
Overall response rate based on RECIST V1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
Overall response (OR) in patients with metastatic Papillary cell renal cancer
Time frame: 18 months
Overall response rate based on RECIST V1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
Overall response (OR)in patients with metastatic renal cell cancer -Biomarker enrichment phase
Time frame: 11 months
Overall response rate based on RECIST v1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
12 secondary outcomes
De-escalation phase - PK-Cmax measurement
Time frame: 14 months
De-escalation phase - PK-Tmax measurement
Time frame: 14 months
De-escalation phase -PK AUC (0-t) measurement
Time frame: 14 months
De-escalation phase - PK AUCs measurement
Time frame: 14 months
De-escalation phase -PK Css measurement
Time frame: 14 months
De-escalation phase -PK Css min measurement
Time frame: 14 months
Expansion Phase (IIa) -Identify Progression free survival (PFS)
Time frame: 18 months
Expansion Phase (IIa) -Identify overall Survival (OS)
Time frame: 18 months
Expansion Phase (IIa) -Identify duration of response
Time frame: 18 months
Biomarker positive patient analysis
Time frame: 11 months
Biomarker positive patient analysis
Time frame: 11 months
Expansion Phase (IIa) -Best Response
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2024.
- Results publicationPowles T et al. CALYPSO: A three-arm randomized phase II study of durvalumab alone or with savolitinib or tremelimumab in previously treated advanced clear cell renal cancer. Journal of Clinical Oncology 40, no. 17_suppl (June 10, 2022) LBA4503-LBA4503
- Results publication: PubMed 36809050Suarez C, Larkin JMG, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite F, Ralph C, Srinivasan G, Mendez-Vidal MJ, Hartmaier R, Markovets A, Prendergast A, Szabados B, Mousa K, Powles T. Phase II Study Investigating the Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer (CALYPSO). J Clin Oncol. 2023 May 10;41(14):2493-2502. doi: 10.1200/JCO.22.01414. Epub 2023 Feb 21.
- Results publicationSuarez Rodriguez et al. Overall survival results for durvalumab and savolitinib in metastatic papillary renal cancer. Journal of Clinical Oncology 2020 38:6_suppl, 619-619.
- Results publicationSuarez Rodriguez et al Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer. J Clin Oncol 39, 2021 (suppl 15; abstr 4511).
- Derived from this study: PubMed 41861260Jackson-Spence F, Larkin J, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite FC, Ralph C, Srinivasan G, Mendez-Vidal MJ, Childress M, Li W, Boyle P, Gasco A, Markovets A, Hartmaier R, Ackerman C, Szabados BE, Priyadarshini G, Jamal F, Powles T, Suarez C. CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer. J Clin Oncol. 2026 Apr 20;44(12):1076-1082. doi: 10.1200/JCO-25-01840. Epub 2026 Mar 20.
- Individual participant dataSharing planned: No
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Renal Cell Carcinoma
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Savolitinib, MEDI4736 and Tremelimumab in people with Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma, run by Queen Mary University of London at 1 site in United Kingdom.
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 16 inclusion and 31 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: finished, as of the sponsor's last update on 4 Nov 2024. 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 Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Identify Dose Limiting Toxicity -Phase Ib (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02819596, which also lists 5 linked publications.
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 4 Nov 2024.