Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MK-1084, [14C]Calderasib
Calderasib · 10 trials · 7 indications
PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.
DFS is the time from randomization to any recurrence (local, locoregional, regional, or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.
PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.
A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration.
An AE is 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.
An AE is 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.
PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.
A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration, excluding toxicities clearly not related to the drug.
An AE is 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.
An AE is 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.
ORR is defined as the percentage of participants with 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. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
ORR is defined as the percentage of participants with 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.
DLT will be defined as any drug-related AE observed during the DLT evaluation period (up to 42 days) that results in a change to a given dose or a delay in initiating the next treatment.
An AE is 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. The number of participants that experience AEs will be reported.
Blood samples will be collected to determine the AUC0-inf of midazolam.
Blood samples will be collected to determine the AUC0-last of midazolam.
Blood samples will be collected to determine the AUC0-24hr of midazolam.
Blood samples will be collected to determine the Cmax of midazolam.
Blood samples will be collected to determine the Tmax of midazolam.
Blood samples will be collected to determine the t1/2 of midazolam.
Blood samples will be collected to determine the CL/F of midazolam.
Blood samples will be collected to determine the Vz/F of midazolam.
Blood samples will be collected to determine the AUC0-inf of digoxin.
Blood samples will be collected to determine the AUC0-last of digoxin.
Blood samples will be collected to determine the AUC0-24hr of digoxin.
Blood samples will be collected to determine the Cmax of digoxin.
Blood samples will be collected to determine the Tmax of digoxin.
Blood samples will be collected to determine the t1/2 of digoxin.
Blood samples will be collected to determine the CL/F of digoxin.
Blood samples will be collected to determine the Vz/F of digoxin.
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT will be reported.
| Arm | Type | Description |
|---|---|---|
| Calderasib + Durvalumab | EXPERIMENTAL | Participants will receive calderasib and durvalumab. |
| Placebo + Durvalumab | ACTIVE_COMPARATOR | Participants will receive placebo to calderasib and durvalumab. |
| Calderasib + MK-3475A | EXPERIMENTAL | Participants receive calderasib daily (qd) and MK-3475A every 6 weeks (q6w) for up to 9 doses. |
| Placebo + MK-3475A | ACTIVE_COMPARATOR | Participants receive placebo qd and MK-3475A q6w for up to 9 doses. |
| Calderasib + Pembrolizumab (+) Berahyaluronidase alfa | EXPERIMENTAL | Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) plus calderasib until discontinuation criterion is met. |
| Pembrolizumab (+) Berahyaluronidase alfa + Chemotherapy | ACTIVE_COMPARATOR | Participants will receive pembrolizumab (+) berahyaluronidase alfa at a fixed dose subcutaneously on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) and pemetrexed via intravenous (IV) infusion at a dose of 500 mg/m\^2 on days 1 and 22 of cycles 1 and 3 until discontinuation criterion is met PLUS investigator's choice of carboplatin via IV infusion at area under curve (AUC) 5 mg/mL/minute on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks) OR cisplatin via IV infusion at a dose of 75 mg/m\^2 on days 1 and 22 of cycles 1 and 3 (up to 4 doses, approximately 6 weeks). |
| Calderasib + Cetuximab + mFOLFOX6 | EXPERIMENTAL | Participants will receive calderasib orally, cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met. |
| mFOLFOX6 | ACTIVE_COMPARATOR | Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab or bevacizumab biosimilar Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met. |
| Calderasib with Pembrolizumab | EXPERIMENTAL | Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (q3w) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met. |
| Placebo with Pembrolizumab | ACTIVE_COMPARATOR | Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (q3w) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met. |
| Arm A- Pembrolizumab + MK-1084 | EXPERIMENTAL | Participants receive 400 mg of Pembrolizumab every 6 weeks and MK-1084 dose regimen. |
| Arm B- Pembrolizumab + MK-1084 + Cetuximab | EXPERIMENTAL | Participants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and Cetuximab 500 mg/m\^2 every 2 weeks. |
| Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT) | EXPERIMENTAL | Participants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and 4 mg/kg sacituzumab tirumotecan (sac-TMT) every 2 weeks. |
| Calderasib | EXPERIMENTAL | Participants will receive calderasib orally. Per protocol treatment of calderasib has no maximum number of cycles. Participants will be treated until any of the criteria for discontinuation of study intervention are met. |
| Calderasib + Cetuximab | EXPERIMENTAL | Participants will receive calderasib orally. Participants will receive Cetuximab 500 mg/m\^2 via intravenous (IV) infusion once every 2 weeks (Q2W). Per protocol treatment of calderasib and Cetuximab has no maximum number of cycles. Participants will be treated until any of the criteria for discontinuation of study intervention are met. |
| MK-1084 + Patritumab deruxtecan (HER3-DXd) | EXPERIMENTAL | Participants will receive MK-1084 and HER3-DXd until discontinuation due to toxicity, adverse event (AE) or at the discretion of an investigator. |
| MK-1084 + Sacituzumab tirumotecan (Sac-TMT) | EXPERIMENTAL | Participants will receive MK-1084 and sac-TMT until discontinuation due to toxicity, AE or at the discretion of an investigator. |
| MK-1084 + Cetuximab | EXPERIMENTAL | Participants will receive MK-1084 and cetuximab until discontinuation due to toxicity, AE or at the discretion of an investigator. Per amendment 3, the MK-1084 + Cetuximab arm was discontinued. |
| Period 1: Midazolam and Digoxin | EXPERIMENTAL | Participants will receive a single oral dose of midazolam and a single oral dose of digoxin on Day 1. |
| Period 2: Calderasib, Midazolam, and Digoxin | EXPERIMENTAL | A washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first calderasib dosing in Period 2. Participants will receive calderasib once daily on Days 1 through Day 15 with a single oral dose of midazolam on Days 1, 6, and 14 and a single oral dose of digoxin on Days 1 and 11. |
| Arm 1 | EXPERIMENTAL | Participants will receive daily oral escalating doses of up to 800 mg of calderasib until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety. |
| Arm 2 | EXPERIMENTAL | Participants will receive calderasib daily oral escalating dose of up to 800 mg plus pembrolizumab given as a 200 mg intravenous infusion once every 21-day cycle up to a total of 35 cycles (up to \~24 months). Treatment with calderasib will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety. |
| Arm 3 | EXPERIMENTAL | Participants will receive alternate formulation of calderasib until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety. |
| Arm 4 | EXPERIMENTAL | Participants will receive calderasib daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles. |
| Arm 5 | EXPERIMENTAL | Participants will receive calderasib daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle. |
| Arm 6 | EXPERIMENTAL | Participants will receive calderasib daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days. |
| Name | Type | Description |
|---|---|---|
| Calderasib | DRUG | Tablet for oral administration. |
| Durvalumab | BIOLOGICAL | Solution for intravenous (IV) infusion. |
| Placebo to MK-1084 | OTHER | Placebo to MK-1084. |
| MK-3475A | BIOLOGICAL | Fixed dose coformulated product of hyaluronidase/pembrolizumab administered via SC injection. |
| Placebo | DRUG | Placebo oral tablet |
| Pembrolizumab (+) Berahyaluronidase alfa | BIOLOGICAL | Administered as a SC injection |
| Pemetrexed | DRUG | Administered as an IV Infusion |
| Cisplatin | DRUG | Administered as an IV Infusion |
| Carboplatin | DRUG | Administered as an IV Infusion |
| Oxaliplatin | DRUG | Per label |
| Leucovorin/levofolinate calcium | DRUG | Per label |
| 5-Fluorouracil | DRUG | Per label |
| Cetuximab | BIOLOGICAL | Per label |
| Bevacizumab | DRUG | Per label |
| Bevacizumab biosimilar | DRUG | Per label |
| Pembrolizumab | BIOLOGICAL | IV infusion |
| MK-1084 | DRUG | Oral Administration |
| Sacituzumab tirumotecan (sac-TMT) | BIOLOGICAL | Injection powder for intravenous infusion |
| Rescue medication | DRUG | Participants receive the following rescue medications, per approved product label, as premedication to study treatment to prevent hypersensitivity and/or infusion reactions: diphenhydramine (or equivalent histamine-1 \[Hl\] receptor antagonist), H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, and granulocyte colony-stimulating factor (G-CSF). A steroid mouthwash (dexamethasone or equivalent) will be given as prophylaxis for stomatitis/oral mucositis. |
| Patritumab deruxtecan | BIOLOGICAL | IV infusion |
| Sacituzumab tirumotecan | BIOLOGICAL | IV Infusion |
| Rescue Medications | DRUG | Participants receive rescue medication at the investigator's discretion for prevention of nausea and vomiting, per approved product label. Recommended rescue medications are histamine-1 (H1) receptor antagonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent), 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, neurokinin 1 (NK-1) receptor antagonist and corticosteroid. |
| Midazolam | DRUG | Oral administration |
| Digoxin | DRUG | Oral administration |
| leucovorin | DRUG | Per label |
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histological or cytological diagnosis of locally advanced, unresected Stage II (node-positive) to III non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology. * Has completed d...
Calderasib is an investigational small molecule drug being developed by Merck & Company, Inc. (MRK) for oncology. It is being studied in advanced solid tumors, colon adenocarcinoma, malignant neoplasms, and non-small cell lung cancer. Calderasib is a KRAS G12C inhibitor and is currently in Phase 1 clinical development.
Calderasib is being studied for the treatment of advanced solid tumors, colon adenocarcinoma, malignant neoplasms, and non-small cell lung cancer. It is an investigational therapy and has not been approved for any indication. Clinical trials are enrolling patients with KRAS G12C-mutated cancers, including non-small cell lung cancer.
Calderasib targets KRAS G12C, a mutant form of the KRAS protein. KRAS G12C is a protein target, and Calderasib is a small molecule designed to inhibit this specific mutation. The drug is being evaluated in biomarker-selected patient populations whose tumors carry the KRAS G12C mutation.
Calderasib is being developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is the sponsor of the clinical trials evaluating Calderasib, also known as MK-1084, in oncology indications including non-small cell lung cancer and advanced solid tumors.
Calderasib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. There are 5 clinical trials total, with 4 currently active and 1 completed, enrolling a total of 1,761 participants across the studies.
Calderasib is being studied in several trials, including NCT07554339, a Phase 3 trial with durvalumab in non-small cell lung cancer, and NCT07431827, a Phase 3 trial in resected KRAS G12C-mutant NSCLC. Other trials include NCT07286149 (Phase 1) and NCT07252739 (Phase 2) in non-small cell lung cancer.
Yes, Calderasib is also known as MK-1084 and [14C]Calderasib. MK-1084 is the Merck development code for Calderasib, and [14C]Calderasib refers to the carbon-14 labeled form used in research. These names refer to the same investigational KRAS G12C inhibitor.