Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Calderasib · 14 trials · 8 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.
OS is defined as the time from randomization to death due to any cause.
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.
Blood samples will be collected at multiple time points to determine the AUC0-inf of rosuvastatin
Blood samples will be collected at multiple time points to determine the Cmax of rosuvastatin
Blood samples will be collected at multiple time points to determine the AUC0-inf of metformin
Blood samples will be collected to determine the AUC0-last of calderasib in plasma.
Blood samples will be collected to determine the AUC0-inf of calderasib in plasma.
Blood samples will be collected to determine the AUC0-24 of calderasib in plasma.
Blood samples will be collected to determine the Cmax of calderasib in plasma.
Blood samples will be collected to determine the Tmax of calderasib in plasma.
Blood samples will be collected to determine the t1/2 of calderasib in plasma.
Blood samples will be collected to determine the CL/F of calderasib in plasma.
Blood samples will be collected to determine the Vz/F of calderasib in plasma.
Blood samples will be collected to determine the AUC0-inf of calderasib.
Blood samples will be collected to determine the AUC0-last of calderasib.
Blood samples will be collected to determine the AUC0-24 of calderasib.
Blood samples will be collected to determine the C24 of calderasib.
Blood samples will be collected to determine the Cmax of calderasib.
Blood samples will be collected to determine the Tmax of calderasib.
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.
Bood samples will be collected to determine the AUC0-inf of calderasib in plasma.
Blood samples will be collected to determine the AUC0-last of calderasib in plasma.
Blood samples will be collected to determine the AUC0-24 of plasma calderasib in plasma.
Blood samples will be collected to determine the Cmax of calderasib in plasma.
Blood samples will be collected to determine the C24 of calderasib in plasma.
Blood samples will be collected to determine the Tmax of calderasib in plasma.
Blood samples will be collected to determine the t1/2 of calderasib in plasma.
Blood samples will be collected to determine the CL/F of calderasib in plasma.
Blood samples will be collected to determine the Vz/F of calderasib in plasma.
Blood samples will be collected to determine the AUC0-inf/Total Radioactivity Ratio of calderasib in plasma.
Urine samples will be collected to determine the Aeu of calderasib
Urine samples will be collected to determine the cumulative Ae of calderasib.
Urine samples will be collected to determine the feu of calderasib.
Urine samples will be collected to determine the cumulative feu of calderasib.
Feces samples will be collected to determine the Aef of calderasib.
Feces samples will be collected to determine the cumulative Aef of calderasib.
Feces samples will be collected to determine the fef of calderasib.
Feces samples will be collected to determine the cumulative fef of calderasib.
Blood samples will be collected to determine the metabolites of calderasib.
Urine samples will be collected to determine the metabolites of calderasib.
Feces samples will be collected to determine the metabolites of calderasib.
Blood samples will be collected to determine the AUC0-Inf of calderasib.
Blood samples will be collected to determine the AUC0-inf of calderasib.
Blood samples will be collected to determine the Cmax of calderasib.
Blood samples will be collected to determine the AUC0-last of calderasib.
Blood samples will be collected to determine the AUC0-inf of calderasib.
Blood samples will be collected to determine the AUC0-24 of calderasib.
Blood samples will be collected to determine the Cmax of calderasib.
Blood samples will be collected to determine the C24 of calderasib.
Blood samples will be collected to determine the tlag of calderasib.
Blood samples will be collected to determine the Tmax of calderasib.
Blood samples will be collected to determine the t1/2 of calderasib.
Blood samples will be collected to determine the CL/F of calderasib.
Blood samples will be collected to determine the Vz/F of calderasib.
Blood samples will be collected to determine the AUC0-inf of calderasib.
Blood samples will be collected to determine the Cmax of calderasib.
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.
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE 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. |
| 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. |
| Rosuvastatin + metformin | EXPERIMENTAL | Participants will receive rosuvastatin plus metformin |
| Rosuvastatin + metformin + Calderasib | EXPERIMENTAL | Participants will receive rosuvastatin plus metformin plus calderasib |
| Panel A: Severe RI | EXPERIMENTAL | Participants with severe RI will be administered a single oral dose of calderasib on Day 1 under fasting conditions. |
| Panel B: Moderate RI | EXPERIMENTAL | Participants with moderate RI will be administered a single oral dose of calderasib on Day 1 under fasting conditions. |
| Panel C: Healthy | EXPERIMENTAL | Healthy participants will be administered a single oral dose of calderasib on Day 1 under fasting conditions. |
| 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. |
| Carbon-14 radiolabeled [14C] MK-1084 | EXPERIMENTAL | Participants receive single oral dose of calderasib on Day 1. |
| Part 1: Calderasib + Itraconazole | EXPERIMENTAL | Part 1: In Period 1 participants receive a single dose of calderasib on Day 1 under fasting conditions. In Period 2 participants receive itraconazole once daily (QD) for 7 consecutive days (Day 1 - Day 7), plus a single dose of calderasib administered approximately 2 hours after itraconazole dosing on Day 5. There will be a washout of at least 7 days between dosing in Period 1 and the first dose in Period 2. |
| Part 2: Calderasib + Phenytoin | EXPERIMENTAL | Part 2: In Period 1 participants receive a single dose of calderasib on Day 1 under fasting conditions. In Period 2 participants receive phenytoin three times daily (TID) for 14 consecutive days (Day 1 - Day 14), plus a single dose of calderasib co-administered on the morning of Day 13. There will be a washout of at least 7 days between dosing in Period 1 and the first dose in Period 2. |
| Calderasib Treatment A | EXPERIMENTAL | Participants will receive calderasib on Day 1 on an empty stomach |
| Calderasib Treatment B | EXPERIMENTAL | Participants will receive calderasib on Day 1 after a high-fat/high-calorie breakfast |
| Calderasib Treatment C | EXPERIMENTAL | Participants will receive calderasib Formulation 1 on Day 1 |
| Calderasib Treatment D | EXPERIMENTAL | Participants will receive calderasib Formulation 2 on Day 1 |
| Calderasib Treatment E | EXPERIMENTAL | Participants will receive calderasib without a PPI on Day 1 |
| Calderasib Treatment F | EXPERIMENTAL | Participants will receive calderasib with a PPI on Day 5 |
| 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 |
| Rosuvastatin | DRUG | Oral tablet |
| Metformin | DRUG | Oral tablet |
| Midazolam | DRUG | Oral administration |
| Digoxin | DRUG | Oral administration |
| [14C]Calderasib | DRUG | Oral administration |
| Itraconazole | DRUG | Oral solution |
| Phenytoin | DRUG | Oral capsule (extended) |
| PPI | DRUG | Oral Capsule |
| 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 being studied for the treatment of KRAS mutant advanced solid tumors, including colon adenocarcinoma and non-small cell lung cancer. It is also being evaluated in healthy volunteers for pharmacokinetic studies. The drug is in Phase 1 clinical development and has not been approved by the FDA.
Calderasib is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting multiple Phase 1 clinical trials to evaluate the drug's safety, tolerability, and pharmacokinetics in patients with advanced solid tumors and in healthy participants.
Calderasib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The drug has received a Breakthrough Therapy designation from the FDA, which is intended to expedite the development and review of drugs for serious conditions.
Calderasib is being studied in several Phase 1 trials, including NCT05067283, which is recruiting patients with KRAS mutant advanced solid tumors. Other trials include NCT06619314, NCT06719557, and NCT07222098, which are completed studies in healthy volunteers to evaluate the effects of food, drug interactions, and concomitant medications.
Yes, Calderasib is also known as MK-1084. Clinical trials such as NCT05067283, which is titled 'A Study of Calderasib (MK-1084) in KRAS Mutant Advanced Solid Tumors,' use both names to refer to the same investigational drug being developed by Merck.