A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eisai Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Aug 2022 → 16 Oct 2024

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eisai Ltd

External identifiers

EU CT number

2023-505425-14-00

EudraCT number

2021-001568-10

WHO UTN

U1111-1292-9958

ClinicalTrials.gov

NCT05091346

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Pharmacokinetic, Therapy, Pharmacodynamic, Dose response, Efficacy

Phase 1b part:
• To assess the safety and tolerability of E7386 in combination with pembrolizumab in subjects with previously treated selected solid tumors
• To determine the RP2D of E7386 in combination with pembrolizumab
Phase 2 part:
• To assess the ORR of E7386 in combination with pembrolizumab (melanoma, colorectal cancer [CRC], hepatocellular carcinoma [HCC]) or of E7386 in combination with pembrolizumab plus lenvatinib (HCC) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary objectives 2

1. Phase 1b part only: • To assess tumor response according to RECIST 1.1
2. Phase 1b and Phase 2 parts: •To assess duration of response (DOR) according to RECIST 1.1 per tumor cohort •To assess the disease control rate (DCR: the proportion of subjects with complete response [CR], partial response [PR], or stable disease [SD] after ≥5 weeks from the first dose) according to RECIST 1.1 per tumor cohort •To assess the clinical benefit rate (CBR: the proportion of subjects with CR, PR, or durable SD [duration of SD ≥23 weeks]) according to RECIST 1.1 per tumor cohort •To assess the safety and tolerability of E7386 in combination with pembrolizumab and E7386 in combination with pembrolizumab plus lenvatinib •To evaluate the pharmacokinetic (PK) profile of E7386 when co-administered either with pembrolizumab or with the combination of pembrolizumab plus lenvatinib •To evaluate the PK profile of lenvatinib when co-administered with E7386 plus pembrolizumab •To determine the optimal dose level of E7386 in combination with pembrolizumab plus lenvatinib

Conditions and MedDRA coding

colorectal cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
2. Male or female, age ≥18 years (or any age ≥18 years as determined by country legislation) at the time of informed consent.
3. Life expectancy of ≥12 weeks.
4. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) selected solid tumor for which prior standard systemic therapy has failed. Selected tumor types: melanoma (excluding uveal melanoma), CRC, HCC.
5. For Melanoma Cohort only (Phase 2 part), subject must have: a. Unresectable Stage III or Stage IV melanoma, per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy. b. At least one measurable lesion by computer tomography (CT) or magnetic imaging resonance (MRI) based on RECIST 1.1 (cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol but may be considered as nontarget lesions).  Lesions in a previously irradiated area should not be considered measurable unless there has been documented growth of the lesions since the completion of radiotherapy. c. Progressed on or after prior treatment with one anti-PD-1/PD-L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 progression is defined as:  Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb (eg, pembrolizumab, nivolumab, nivolumab plus ipilimumab) and  Has demonstrated disease progression after PD-1/PD-L1 as defined by RECIST v1.1. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/PD-L1 mAb (refractory disease). The initial evidence of disease progression is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented progressive disease, in the absence of rapid clinical progression.  This determination is made by the investigator. Once progressive disease is confirmed, the initial date of disease progression documentation will be considered the date of disease progression. d. Received only 1 or, if BRAF mutation positive, 2 lines of therapy in the locally advanced or metastatic setting prior to study enrollment. Note: Adjuvant anti-PD- 1/PD-L1 mAb/ BRAF inhibitor treatment will be counted as prior line of treatment if relapse occurred during active treatment or within 12 weeks of treatment discontinuation. e. No restriction with regards to PD-L1 and BRAF status f. In case melanoma is known to be BRAF mutation positive, subjects must have progressed on one prior BRAF inhibitor
6. For CRC Cohort only (Phase 2 part), subjects must have received at least two prior systemic therapies from the following, in adjuvant and/or metastatic setting, if approved and locally available (not exceeding 4 lines of therapies in the metastatic setting, progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment): Note: Adjuvant chemotherapy counts as prior systemic treatment in the metastatic setting if there is documented disease progression within 6 months of treatment completion. Note: If a subject is determined to be intolerant to prior standard treatment, the subject must have received at least of 2 cycles of that therapy. a. Fluoropyrimidine, irinotecan and oxaliplatin Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment. Note: Subjects who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, eg, fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) or fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX), may be eligible after discussion with the Sponsor. b. Chemotherapy with or without an anti-VEGF mAb (eg, bevacizumab) c. Chemotherapy with anti-EGFR mAb (cetuximab or panitumumab) for subjects with RAS (KRAS/NRAS) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT subjects with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible d. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors.
7. Subjects with HCC (Phase 2 part) must have: a. A diagnosis of HCC that is histologically or cytologically confirmed (excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors) or clinically confirmed according to American Association for the Study of Liver Disease criteria in cirrhotic subjects. Subjects without cirrhosis require histological confirmation of diagnosis. b. Stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment) or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging System and Child-Pugh class A only. c. Subjects must have received only one prior line of systemic therapy in the locally advanced or metastatic setting, and must have progressed on treatment with an anti- PD-1/PD-L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. Note: Subjects must have received at least 2 doses of the anti- PD-1/PD-L1 mAb.
8. For subjects with HCC: a. In case of hepatitis B surface antigen (HBsAg) (+) subjects: Antiviral therapy for hepatitis B virus (HBV) must be given for at least 3 months prior to the first dose of study drug, and HBV viral load must be less than 100 IU/mL prior to the first dose of study drug. ◦ Subjects who are HBsAg (+) and on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy while on study drug. ◦ Subjects without HBV prophylaxis who are anti-hepatitis B core antibody (HBcAb) (+) and/or anti- HBsAb (+) but negative for HBsAg and HBV DNA do not require prophylaxis. ◦ Subjects with HBV prophylaxis who are anti-HBcAb (+) and/or anti- HBsAb (+) but negative for HBsAg and HBV DNA should continue the prophylaxis. ◦ All the subjects above need monitoring with HBV DNA every 3 weeks while on study drug. b. Therapy for hepatitis C virus (HCV) must be completed at least 4 weeks prior to first dose of study drug in case of hepatitis C subjects who are on active HCV treatment. Hepatitis C subjects who are untreated or uncured may also be enrolled.
9. Triplet treatment cohorts only: Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening/Baseline and no change in antihypertensive medications within 1 week before starting treatment in this study.
10. ECOG PS of 0 to 1.
11. Subject must have disease progression on current or since the last anticancer treatment.
12. At least one measurable lesion by CT or MRI based on RECIST 1.1 confirmed by the investigator: a. At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using CT/MRI. b. Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolization (TACE)/transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
13. Agree to consent for archival tumor tissue or a newly obtained biopsy tissue must be acquired prior to the first dose of study drug for biomarker analysis. Formalin-fixed paraffin embedded tissue block is preferred to slide. Newly obtained biopsy samples are preferred to archival tissue. In the case archival tissue cannot be provided, subjects with inaccessible tumors for biopsy specimens can be enrolled without a biopsy upon consultation and agreement by the Sponsor. For subjects with melanoma, in addition to pretreatment biopsy, C2D1 biopsy will be collected from the pre-designated non-target lesion, if they have recovered adequately from the biopsy taken prior to starting therapy). Note: If subject has only measurable lesion and no accessible non measurable disease, the subject can be enrolled without a biopsy upon consultation and agreement by the Sponsor). Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from when the slides are cut (details pertaining to the tumor tissue submission can be found in the Laboratory Manual).
14. Adequate renal function defined as creatinine clearance ≥30 mL/min per the Cockcroft and Gault formula (creatinine clearance ≥40 mL/min for subjects with HCC only)
15. Adequate bone marrow function: a. ANC ≥1.5 × 109/L b. Platelets ≥100 × 109/L (platelets ≥75 × 109/L for subjects with HCC only). c. Hemoglobin ≥9.0 g/dL (criterion must be met without packed red blood cell [pRBC] transfusion within the prior 2 weeks). Subjects can be on stable dose of erythropoietin (approximately ≥3 months).
16. Adequate liver function: a. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤1.5 (≤2.3 for subjects with HCC only) b. TBL ≤1.5 × ULN (≤2.0 × ULN for subjects with HCC only) c. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN for subjects with HCC only or if subject has liver metastasis).
17. All AEs due to previous anticancer therapy must have returned to Grade 0–1 except for alopecia and Grade 2 peripheral neuropathy.
18. Subjects must agree to take Vitamin D continuous supplementation as per local institutional guideline/ investigator’s clinical discretion if their 25-hydroxyvitamin D levels are less than 10 ng/mL.
19. Adequate serum mineral level: a. Calcium (albumin-corrected) within normal range b. Potassium within normal reference range c. Magnesium ≥1.2 mg/dL or 0.5 mmol/L.

Exclusion criteria 31

1. History of other active malignancy (except for original disease, or definitively treated basal or squamous cell skin carcinoma, carcinoma in-situ of the bladder or cervix) within the past 24 months prior to the first dose of study drug.
2. Major surgery within 21 days prior to starting study drug or minor surgery (ie, simple excision) within 1 week (subject must also have recovered from any surgery-related toxicities to less than CTCAE Grade 2). Note for triplet treatment cohorts: Adequate wound healing after major surgery must be assessed clinically.
3. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition or procedure that might impair the bioavailability of E7386 or lenvatinib (only for triplet treatment cohorts) in the opinion of the investigator(s).
4. Any of the cardiac conditions as follows: a. New York Heart Association (NYHA) congestive heart failure Class II or above b. Significant cardiovascular impairment within 6 months (12 months for triplet treatment cohorts) of the first dose of study drug: unstable angina, myocardial infarction, cerebrovascular accident (CVA), or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted. c. Prolongation of corrected QT Fridericia (QTcF) interval to >450 msec d. Left ventricular ejection fraction (LVEF) below the institutional normal range, as determined by multi-gated acquisition (MUGA) or echocardiogram (ECHO)
5. Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to study drug administration. The subject can receive diuretic drugs as needed per the treating physician, outside of the abovementioned conditions. Consult with the Sponsor if the subject has more than trivial/trace fluid accumulation.
6. Prior treatment with E7386, or has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte associated protein-4 (CTLA)-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immunerelated (ir)AE.
7. Subjects who have received treatments below before first study drug administration: a. Any prior anticancer treatment or investigational drug: within 4 weeks or 5 times the half-life, whichever is shorter b. Any investigational device: within 4 weeks. c. Radiotherapy: within 2 weeks of start of study drug. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. d. Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. e. Has not recovered adequately from the toxicity and/or complications from the intervention if subject received major surgery prior to starting study drug. f. Drugs or supplements that are known potent cytochrome P450 3A (CYP3A) inducers/inhibitors or sensitive substrates within 4 weeks before study drug administration. g. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen within 4 weeks.
8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (at a dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
9. Subjects with CNS metastases are not eligible unless they are previously treated, are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), and clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
10. Diagnosed meningeal carcinomatosis
11. Has severe hypersensitivity (Grade ≥3) to study drugs and/or any of its excipients including previous clinically-significant hypersensitivity reaction to treatment with another mAB.
12. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
13. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
14. Active infection requiring systemic treatment.
15. Active viral hepatitis (B or C) as demonstrated by positive serology for subjects with melanoma and CRC. For subjects with HCC: - Has dual active HBV infection (HBsAg [+] and /or detectable HBV DNA) and HCV infection (anti-HCV Ab [+] and detectable HCV RNA) at study entry.
16. Known to be human immunodeficiency virus (HIV) positive. (Note: the Sponsor has evaluated whether to include subject with HIV. Given that this is the first combination study of E7386 with pembrolizumab and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several antiretroviral therapies have drug-drug interaction with cytochrome P450 3A4 (CYP3A) substrates, the Sponsor has decided not to include these subjects at the current time. However, further considerations will be made moving forward based on new emerging data).
17. Evidence of current COVID-19 infection or ongoing unrecovered sequelae of COVID-19 infection.
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
19. Has a known psychiatric or substance abuse disorder that would interfere with the subject’s ability to cooperate with the requirements of the study.
20. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject’s safety or interfere with the study assessments.
21. Scheduled for major surgery during the study.
22. Any of the bone disease/conditions as follows: a. see protocol b. Metabolic bone disease, such as hyperparathyroidism, Paget’s disease or osteomalacia. c. Symptomatic hypercalcemia requiring bisphosphonate therapy. d. History of any fracture within 6 months prior to starting study drug. e. History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less). f. Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline. g. Any condition requiring orthopedic intervention. h. Bone metastases not being treated with a bisphosphonate or denosumab. Subject may be included if treatment with bisphosphonate or denosumab have been started at least 14 days prior to Cycle 1. Subjects with previous solitary bone lesions controlled with radiotherapy are eligible.
23. Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell transplant requiring chronic immunosuppressant therapy necessary to prevent graft rejection).
24. Received blood/platelet transfusion or G-CSF within 4 weeks before study entry.
25. See protocol
26. Females of childbearing potential who: Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: a. total abstinence (if it is their preferred and usual lifestyle)* b. an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) c. a contraceptive implant d. an oral contraceptive (subject must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 120 days after study drug discontinuation.) e. have a vasectomized partner with confirmed azoospermia f. do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for at least 120 days after study drugs discontinuation (corresponding to the time needed to eliminate any study drug). For sites outside of the EU and UK, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, ie, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). *Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study.
27. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (ie, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 5 times the half-life of the study drug plus 120 days after study drug discontinuation). No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation.
28. For subjects with melanoma only, subjects with ocular melanoma are excluded. Note: Subjects with mucosal melanoma will not exceed 20% of the enrolled subjects in melanoma cohort in Phase 2.
29. For subjects with CRC only, subject is excluded if: a. has a tumor that is MSI H/dMMR positive b. has received prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
30. For subjects with HCC only, subject is excluded if: a. clear invasion to bile duct b. has had esophageal or gastric variceal bleeding within the last 6 months. Subjects in triplet treatment cohorts will be screened for esophageal or gastric varices unless such screening has been performed in the past 3 months before first dose of treatment. If varices are present, they should be treated according to institutional standards before starting study intervention; esophageal or gastric varices that require interventional treatment within 28 days prior to first dose of study drug are excluded. c. history of hepatic encephalopathy within 6 months prior starting study drug unresponsive to therapy within 3 days. Subjects on rifaximin or lactulose during screening to control their hepatic encephalopathy are not allowed
31. For subjects in the triplet treatment cohorts only: a. Proteinuria >1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1 g/24 hours will be ineligible b. Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR monitoring (eg, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted c. Clinically significant hemoptysis from any source or tumor bleeding within 3 weeks prior to the first dose of study drug d. Preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1b part: Safety related endpoints including DLT
2. Phase 2 part: ORR is defined as the proportion of subjects who have best overall response (BOR) of confirmed CR or PR per RECIST 1.1

Secondary endpoints 7

1. BOR per RECIST 1.1 (for Phase 1b part).
2. DOR is defined as the time from the first documentation of CR or PR to the first documentation of disease progression or death due to any cause (whichever occurs first), in subjects with confirmed CR or PR per RECIST 1.1
3. DCR is defined as the proportion of subjects who have a BOR of confirmed CR or PR, or SD: after ≥5 weeks from the first dose) per RECIST 1.1
4. CBR is defined as the proportion of subjects who have a BOR of confirmed CR or PR, or durable SD (duration of SD ≥23 weeks) per RECIST 1.1
5. Safety and tolerability (eg, treatment-emergent adverse events, treatment-related adverse events) for E7386 in combination with pembrolizumab and safety and tolerability including DLTs for E7386 in combination with pembrolizumab plus lenvatinib
6. PK profile of E7386 when co-administered either with pembrolizumab (doublet treatment cohorts) or with pembrolizumab plus lenvatinib (triplet treatment cohorts)
7. PK profile of lenvatinib in combination with E7386 and pembrolizumab (triplet treatment cohorts)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eisai Limited

Sponsor organisation

Eisai Limited

Address

European Knowledge Center, Mosquito Way Mosquito Way

City

Hatfield

Postcode

AL10 9SN

Country

United Kingdom

Scientific contact point

Organisation

Eisai Limited

Contact name

EU Medical Information

Public contact point

Organisation

Eisai Limited

Contact name

EU Medical Information

Third parties 15

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications