Advanced Solid Tumors, Biliary Tract Cancers, Colorectal Cancer, Gastric Cancer, Glioblastoma, Ovarian Cancer, Pancreatic Cancer, Triple Negative Breast Cancer
Conditions
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2), tyrosine kinase inhibitor (TKI), multiple TKI, Vascular Endothelial Growth Factor Receptor (VEFG), Fibroblast Growth Factor (FGF), Platelet-Derived Growth Factor (PDGF)
Brief summary
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC), or pancreatic cancer.
Interventions
BIOLOGICALPembrolizumab
Administered as an IV infusion on Day 1 Q3W.
DRUGLenvatinib
Administered orally once a day during each 21-day cycle.
Sponsors
Merck Sharp & Dohme LLC
Eisai Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer * Must have progressed on or since the last treatment * Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR * Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated * Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib, or refrain from heterosexual intercourse during this period * Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of study treatment initiation * Has adequate organ function For Triple Negative Breast Cancer Participants: * Has received one or 2 prior lines of therapy * Has Lactate Dehydrogenase (LDH) \<2.0 x Upper Limit of Normal (ULN) * Has locally determined results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 tumor analyses For Ovarian Cancer Participants: \- Has primary ovarian cancer and has received 3 prior lines of therapy. For Gastric Cancer Participants: \- Has received 2 prior lines of therapy. Note: Gastric cancer will include participants with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with squamous cell carcinoma histology are not eligible For Colorectal Cancer Participants: \- Has received 2 prior lines of therapy For GBM Participants: * Has failed initial systemic therapy for newly diagnosed GBM * Have the following time periods elapsed before the projected start of scheduled study treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent, 5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies and 1 week for cancer vaccines * Be neurologically stable (e.g. without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable * Has histologically confirmed World Health Organization (WHO) Grade IV GBM * Has locally determined result for O\^6-methylguanine-DNA methyltransferase (MGMT) analysis For Biliary Tract Cancer Participants: * Has received 1 prior line of therapy * Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6 For Pancreatic Cancer Participants: * Has pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma that is metastatic at enrollment * Has received one or 2 prior lines of therapy * Has received prior therapy with at least 1 (platinum-containing regimen or gemcitabine-containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer
Exclusion criteria
* Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib * Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to all cohorts except the ovarian cancer cohort) * Has radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation. Participants with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on imaging in the BTC cohort are not eligible for enrollment * Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment * Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA), or cardiac arrhythmia associated with hemodynamic instability * Has a history of arterial thromboembolism within 12 months of start of study treatment * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. * Has a serious nonhealing wound, ulcer or bone fracture * Has had major surgery within 3 weeks prior to first dose of study interventions * Has biologic response modifiers therapy (e.g. granulocyte colony-stimulating factor) within 4 weeks before study entry * Has preexisting ≥Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula * Has received prior therapy with lenvatinib, 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 (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], Tumor necrosis factor receptor superfamily, member 4 \[OX 40\], tumor necrosis factor receptor superfamily member 9 \[CD137\]) * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment start * If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment * Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease * Has received a live vaccine within 30 days prior to the first dose of study treatment * Has known intolerance to lenvatinib (and/or any of the excipients) * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment * Has known active CNS metastases and/or carcinomatous meningitis * Has tumors involving the brain stem * Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients * Has an active autoimmune disease that has required systemic treatment in past 2 years * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis * Has an active infection requiring systemic therapy * Has a known history of human immunodeficiency virus (HIV) infection * Has a known history of hepatitis B or known active hepatitis C virus infection * Has a known history of active tuberculosis (TB; Bacillus tuberculosis) * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment * Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell transplant requiring chronic immunosuppressant therapy necessary to prevent graft rejection) For GBM Participants: * Has carcinomatous meningitis * Has recurrent tumor greater than 6 cm in maximum diameter * Has tumor primarily localized to the brainstem or spinal cord * Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease * Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance imaging (MRI) scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans * Has received Optune® TTFields within 2 weeks of study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment | Up to approximately 66 months | ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 by investigator assessment was presented. Per protocol, only data for Cohorts A and B were presented for this endpoint. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | Up to approximately 66 months | ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. For participants with GBM, response was assessed according to RANO criteria whereby ORR was defined as the percentage of participants who had a best overall response of either Complete response (CR): Disappearance of all target lesions or Partial response (PR): sum of products of diameters decreased by ≥50% from baseline value. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 or RANO by BICR was presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint. |
| Number of Participants With One or More Adverse Events (AEs) | Up to approximately 66 months | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one or more AE is presented. |
| Number of Participants Who Discontinued From Study Treatment Due to an AE | Up to approximately 62 months | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued from study treatment due to an AE is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment | Up to approximately 66 months | DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). Disease Control rate per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint. |
| Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | Up to approximately 66 months | DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm\]). The appearance of one or more new lesions is also considered PD.\]). For participants with GBM, response was assessed according to RANO criteria whereby overall response was based on both radiographic response (CR: disappearance of all target lesions, PR: sum of products of diameters \[SPD\] decreased by ≥ 50% from baseline value and SD: SPD \<50% decreased from baseline, but \<25% increased from nadir) and clinical performance status with steroid dose information. The DCR as assessed by BICR is presented. |
| Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment | Up to approximately 66 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. Duration of response per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint. |
| Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | Up to approximately 66 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. For participants with GBM, response will be assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information. DOR assessments were based on blinded central imaging review with confirmation. |
| Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment | Up to approximately 66 months | PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The percentage of participants who experienced PFS per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint. |
| Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | Up to approximately 66 months | PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1 (or RANO for GBM participants), modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For participants with GBM, either radiological progression or clinical deterioration (not attributable to a nontumor-related cause) qualifies as PD. The percentage of participants who experienced PFS per RECIST 1.1 or RANO by BICR is presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint. |
| Overall Survival (OS) | Up to approximately 66 months | OS was defined as the time from the date of study treatment to the date of death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants is presented. |
| Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days. | Blood samples were collected at pre-specified timepoints to determine the AUCss in participants receiving Lenvatinib (Lenva) co-administered with Pembrolizumab (Pembro). AUCss was defined as a measure of drug exposure that was calculated as the product of plasma drug concentration and time after drug administration at steady state. AUCss determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Noncompartmental analysis was used to calculate AUC0ss for each participant. Mean and standard deviation of AUCss were calculated for each cohort. As specified in the protocol, pharmacokinetic analysis was not planned or conducted in Cohorts D2 and G. |
Countries
Argentina, Australia, Canada, Chile, Colombia, France, Germany, Israel, Italy, Russia, South Korea, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
This study was conducted at 85 centers in 17 countries.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) Participants received Pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenvatinib (lenva) 20 mg via oral capsule once a day (QD) up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 31 |
| Cohort B: Ovarian Cancer (Lenva + Pembro) Participants received Pembro 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenva 20 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 31 |
| Cohort C: Gastric Cancer (Lenva + Pembro) Participants received Pembro 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenva 20 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 102 |
| Cohort D1: Colorectal Cancer (Lenva + Pembro) Participants received Pembro 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenva 20 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 107 |
| Cohort D2: Colorectal Cancer (Lenva) Participants received Lenva 24 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 32 |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) Participants received Pembro 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenva 20 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 102 |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) Participants received Pembro 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenva 20 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 103 |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) Participants received Pembro 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (up to 2 years) PLUS Lenva 20 mg via oral capsule QD up to at least 2 years. Participants continued study intervention until progressive disease or unacceptable toxicity. | 103 |
| Total | 611 |
Baseline characteristics
| Characteristic | Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Cohort G: Pancreatic Cancer (Lenva + Pembro) | Total | Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Cohort B: Ovarian Cancer (Lenva + Pembro) | Cohort C: Gastric Cancer (Lenva + Pembro) | Cohort D1: Colorectal Cancer (Lenva + Pembro) | Cohort D2: Colorectal Cancer (Lenva) | Cohort E: Glioblastoma Multiforma (Lenva + Pembro) |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 47 Participants | 213 Participants | 6 Participants | 13 Participants | 34 Participants | 36 Participants | 7 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 56 Participants | 398 Participants | 25 Participants | 18 Participants | 68 Participants | 71 Participants | 25 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 16 Participants | 91 Participants | 6 Participants | 2 Participants | 17 Participants | 19 Participants | 9 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 86 Participants | 441 Participants | 19 Participants | 23 Participants | 64 Participants | 77 Participants | 23 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 1 Participants | 79 Participants | 6 Participants | 6 Participants | 21 Participants | 11 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 8 Participants | 82 Participants | 5 Participants | 4 Participants | 11 Participants | 17 Participants | 2 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 11 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 13 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 0 Participants | 60 Participants | 4 Participants | 4 Participants | 17 Participants | 11 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) White | 71 Participants | 90 Participants | 444 Participants | 22 Participants | 23 Participants | 70 Participants | 71 Participants | 25 Participants | 72 Participants |
| Sex: Female, Male Female | 53 Participants | 42 Participants | 271 Participants | 31 Participants | 31 Participants | 30 Participants | 32 Participants | 14 Participants | 38 Participants |
| Sex: Female, Male Male | 50 Participants | 61 Participants | 340 Participants | 0 Participants | 0 Participants | 72 Participants | 75 Participants | 18 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 27 / 31 | 28 / 31 | 97 / 102 | 97 / 107 | 30 / 32 | 99 / 102 | 98 / 103 | 101 / 103 |
| other Total, other adverse events | 30 / 31 | 31 / 31 | 95 / 99 | 103 / 105 | 29 / 30 | 98 / 101 | 100 / 102 | 101 / 103 |
| serious Total, serious adverse events | 16 / 31 | 19 / 31 | 57 / 99 | 55 / 105 | 12 / 30 | 30 / 101 | 62 / 102 | 49 / 103 |
Outcome results
Primary
Number of Participants Who Discontinued From Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued from study treatment due to an AE is presented.
Time frame: Up to approximately 62 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 5 Participants |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 11 Participants |
| Cohort D2: Colorectal Cancer (Lenva) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 23 Participants |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 19 Participants |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 4 Participants |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 11 Participants |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 20 Participants |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Number of Participants Who Discontinued From Study Treatment Due to an AE | 19 Participants |
Primary
Number of Participants With One or More Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one or more AE is presented.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 31 Participants |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 31 Participants |
| Cohort D2: Colorectal Cancer (Lenva) | Number of Participants With One or More Adverse Events (AEs) | 97 Participants |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 104 Participants |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 30 Participants |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 101 Participants |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 102 Participants |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Number of Participants With One or More Adverse Events (AEs) | 103 Participants |
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment
ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 by investigator assessment was presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment | 22.6 Percentage of Participants |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment | 25.8 Percentage of Participants |
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR)
ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. For participants with GBM, response was assessed according to RANO criteria whereby ORR was defined as the percentage of participants who had a best overall response of either Complete response (CR): Disappearance of all target lesions or Partial response (PR): sum of products of diameters decreased by ≥50% from baseline value. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 or RANO by BICR was presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | 15.2 Percentage of Participants |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | 14.3 Percentage of Participants |
| Cohort D2: Colorectal Cancer (Lenva) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | 6.7 Percentage of Participants |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | 21.8 Percentage of Participants |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | 17.6 Percentage of Participants |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for Glioblastoma Multiforma [GBM] Only), by Blinded Independent Central Review (BICR) | 7.8 Percentage of Participants |
Secondary
Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib
Blood samples were collected at pre-specified timepoints to determine the AUCss in participants receiving Lenvatinib (Lenva) co-administered with Pembrolizumab (Pembro). AUCss was defined as a measure of drug exposure that was calculated as the product of plasma drug concentration and time after drug administration at steady state. AUCss determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Noncompartmental analysis was used to calculate AUC0ss for each participant. Mean and standard deviation of AUCss were calculated for each cohort. As specified in the protocol, pharmacokinetic analysis was not planned or conducted in Cohorts D2 and G.
Time frame: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days.
Population: All allocated participants who received at least 1 dose of study intervention and had data available for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | 3253 ng*hr/mL | Standard Deviation 1029 |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | 3145 ng*hr/mL | Standard Deviation 984 |
| Cohort D2: Colorectal Cancer (Lenva) | Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | 2392 ng*hr/mL | Standard Deviation 803 |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | 2994 ng*hr/mL | Standard Deviation 1143 |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | 2617 ng*hr/mL | Standard Deviation 804 |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib | 2886 ng*hr/mL | Standard Deviation 838 |
Secondary
Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment
DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). Disease Control rate per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment | 51.6 Percentage of Participants |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment | 77.4 Percentage of Participants |
Secondary
Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR
DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm\]). The appearance of one or more new lesions is also considered PD.\]). For participants with GBM, response was assessed according to RANO criteria whereby overall response was based on both radiographic response (CR: disappearance of all target lesions, PR: sum of products of diameters \[SPD\] decreased by ≥ 50% from baseline value and SD: SPD \<50% decreased from baseline, but \<25% increased from nadir) and clinical performance status with steroid dose information. The DCR as assessed by BICR is presented.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 53.5 Percentage of Participants |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 52.4 Percentage of Participants |
| Cohort D2: Colorectal Cancer (Lenva) | Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 56.7 Percentage of Participants |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 57.4 Percentage of Participants |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 64.7 Percentage of Participants |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 37.9 Percentage of Participants |
Secondary
Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. Duration of response per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention and had confirmed complete response or partial response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment | 22.9 Months |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment | 15.3 Months |
Secondary
Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. For participants with GBM, response will be assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information. DOR assessments were based on blinded central imaging review with confirmation.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention and had confirmed complete response or partial response. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 8.3 Months |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 8.3 Months |
| Cohort D2: Colorectal Cancer (Lenva) | Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | NA Months |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 4.6 Months |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 6.2 Months |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 5.8 Months |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of study treatment to the date of death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants is presented.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Overall Survival (OS) | 11.4 Months |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Overall Survival (OS) | 21.3 Months |
| Cohort D2: Colorectal Cancer (Lenva) | Overall Survival (OS) | 4.7 Months |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Overall Survival (OS) | 8.7 Months |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Overall Survival (OS) | 7.9 Months |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Overall Survival (OS) | 8.6 Months |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Overall Survival (OS) | 7.9 Months |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Overall Survival (OS) | 4.3 Months |
Secondary
Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment
PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The percentage of participants who experienced PFS per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment | 4.2 Months |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment | 6.1 Months |
Secondary
Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR
PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1 (or RANO for GBM participants), modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For participants with GBM, either radiological progression or clinical deterioration (not attributable to a nontumor-related cause) qualifies as PD. The percentage of participants who experienced PFS per RECIST 1.1 or RANO by BICR is presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.
Time frame: Up to approximately 66 months
Population: All allocated participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Triple Negative Breast Cancer (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 3.5 Months |
| Cohort B: Ovarian Cancer (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 3.4 Months |
| Cohort D2: Colorectal Cancer (Lenva) | Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 3.4 Months |
| Cohort E: Glioblastoma Multiforma (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 3.0 Months |
| Cohort F: Biliary Tract Cancer (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 4.1 Months |
| Cohort G: Pancreatic Cancer (Lenva + Pembro) | Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR | 2.1 Months |