Infections

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

COVID-19

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Amino Acids

Acalabrutinib

Rabeprazole

Tyrosine Kinase Inhibitors

Proton Pump Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Part 1: Participants will receive Treatment A (100 mg AT suspension in water via NG administration) in Period 1, Treatment B (100 mg acalabrutinib capsule suspension via NG administration) in Period 2, and Treatment C (100 mg AT suspension in water via NG administration plus 20 mg rabeprazole) in Period 3.

Part 2: Participants will receive Treatment D (100 mg AT suspension in water via NG administration) in Period 1 and Treatment A in Period 2.

Part 1: Participants will receive Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3.

Part 2: Participants will receive Treatment A in Period 1 and Treatment D in Period 2.

Participants will receive 100 mg AT suspension in water via NG tube.

Acalabrutinib Treatment A

Participants will receive 100 mg acalabrutinib capsule suspension via NG tube.

Acalabrutinib Treatment B

Participants will receive 100 mg AT suspension in water via NG administration plus 20 mg rabeprazole.

Acalabrutinib Treatment C

Participants will receive 100 mg AT orally.

Acalabrutinib Treatment D

Dr. Rainard Fuhr

This Phase 1 study is being conducted to support the clinical development of acalabrutinib in hospitalized patients who are unable to swallow acalabrutinib tablet or capsule due to respiratory failure, eg, they may require endotracheal intubation for ventilator support and nasogastric (NG) tube placement, and it is important to have a clinically acceptable method to administer acalabrutinib via NG tube.

Part 1 of the study is designed to evaluate relative bioavailability by comparing the pharmacokinetic (PK) of AT suspension in water administered via NG tube with the PK of acalabrutinib capsule suspension in flat COCA-COLA administered via NG tube. Additionally, the PPI effect will be evaluated by comparing the PK of AT suspension in water administered via NG tube plus rabeprazole with the PK of AT suspension in water administered via NG tube.

Part 2 of the study is designed to evaluate the effect of NG administration on AT by comparing the PK of AT suspension in water administered via NG tube with the PK of AT orally administered with water.

Part 1 of the study comprises:

* A screening period of maximum 28 days.
* Three treatment periods during which subjects will reside in the Clinical Unit from Day -2, Treatment Period 1 until at least 48 hours after dosing on Day 1, Treatment Period 3, ie, subjects will be discharged the morning of Day 3, Treatment Period 3.
* A Follow-up Visit within 7 to 10 days after the last dose of acalabrutinib.

There will be a minimum washout period of 4 days between treatment periods. Up to 20 subjects will be included to ensure at least 16 subjects are evaluable. Subjects will be randomized to one of 2 treatment sequences (ABC, BAC) and each subject will receive single doses of 3 treatments under fasted conditions.

Part 2 of the study comprises:

* A screening period of maximum 28 days.
* Two treatment periods during which subjects will reside in the Clinical Unit from Day -2, Treatment Period 1 until at least 48 hours after dosing on Day 1, Treatment Period 2, ie, subjects will be discharged the morning of Day 3, Treatment Period 2.
* A Follow-up Visit within 7 to 10 days after the last dose of acalabrutinib.

There will be a minimum washout period of 4 days between treatment periods. Up to 20 subjects will be included to ensure at least 16 subjects are evaluable. Subjects will be randomized to one of 2 treatment sequences (DA, AD) and each subject will receive single doses of 2 treatments under fasted conditions.

A Study in Healthy Subjects to Assess Bioavailability (Proportion of a Drug Which Enters the Circulation to Have an Active Effect) of Acalabrutinib Tablet and Protonpump Inhibitor Effect (Members of a Class of Medications That Inhibits in Gastric Acid Production) for Rabeprazole

A 2-Part, Phase I, Open-label, Single-dose, Sequential, Randomized, Crossover Study of Acalabrutinib Tablet Suspension Delivered Via Nasogastric Tube in Healthy Subjects to Evaluate Relative Bioavailability and Proton-pump Inhibitor (Rabeprazole) Effect

Qualified researchers can request access to anonymized individual patient-level data from

AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Part 1: Comparison of AUCinf of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of AUCinf of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of AUClast of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of AUClast of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of Cmax of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of Cmax of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of AUC0-24 of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of AUC0-24 of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of tmax of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of tmax of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of t1/2 of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of t1/2 of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of MRT of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of MRT of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of λz of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of λz of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of CL/F of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of CL/F of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of Vz/F of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of Vz/F of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of M:P\[AUC\] of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of M:P\[AUC\] of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of M:P\[Cmax\] of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of M:P\[Cmax\] of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: To evaluate the safety and tolerability of AT suspension administered via NG tube and to evaluate the safety and tolerability of AT suspension via NG tube when co-administered with rabeprazole.

Part 2: To evaluate the safety and tolerability of AT, administered orally.

Parexel

AstraZeneca

Oral BID 360 mg dose (Capsule C: 6 X 60 mg) of ARQ 197 at least 1 hour before or 2 hours after a meal for 7 days

Oral BID 360 mg dose (Tablet: 3 x 120 mg) of ARQ 197 under fed conditions for 7 days

Oral BID 360 mg dose (Capsule D: 3 x 120 mg) of ARQ 197 under fed conditions in the extension phase

Tivantinib (ARQ 197) Capsule

Tivantinib (ARQ 197) Tablet

Tivantinib (ARQ 197) Capsule D, oral

This is a Phase 1, randomized, open label, 2 treatment, 2 period, 2-way crossover study, with an extension phase design in which the steady state PK of ARQ 197 will be investigated using the tablet administered in fed state (test treatment) and capsule administered at least 1 hour before or 2 hours after a meal (reference treatment) in subjects with advanced solid tumors.

Determination of the Relative Bioavailability of ARQ 197 Tablet Formulation With Capsule C Formulation as a Reference in Subjects With Advanced Solid Tumors

An Open-Label, Phase 1, Randomized, Two-Treatment, Two-Period, Two-Way Crossover, Relative Bioavailability Study Of A Capsule And A Tablet Formulation Of ARQ 197 In Subjects With Advanced Solid Tumors

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

The primary endpoints are the area under the concentration time curve from time of dosing until 12 hours post-dose (AUC0-12) and maximum observed concentration in plasma (Cmax) of ARQ 197 following the administration of the tablet (fed conditions) and capsule formulation (at least 1 hour before or 2 hours after a meal).

Time until Cmax (tmax), apparent oral clearance (CL/F), and apparent volume of distribution (V/F) of ARQ 197, and if possible, minimum observed concentration (Cmin) and average observed concentration (Cavg) following the administration of the tablet (fed conditions) and capsule formulation (at least 1 hour before or 2 hours after a meal)

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

ICON Clinical Research

Daiichi Sankyo

Trametinib

Dimethyl Sulfoxide

Protective Agents

Antioxidants

Subjects will receive Treatment A in Period 1 or 2 as single oral dose on Day 1 of Period 1 or 2 in fasting condition with water.

Subjects will receive Treatment B in Period 1 or 2 as single oral dose on Day 1 of Period 1 or 2 in fasting condition with water.

Each tablet contains GSK1120212B equivalent to 2 mg of GSK1120212 as drug substance. The coated tablets have a standard DMSO content of theoretical 11.3%.

GSK1120212B (Standard DMSO content)

Each tablet contains GSK1120212B equivalent to 2 mg of GSK1120212 as drug substance. The coated tablets have a lower DMSO content approximately 9.5%.

GSK1120212B (Lower DMSO content)

GSK Clinical Trials

This is an open-label, randomized, single-dose, 2-treatment, 2-period, 2-way crossover study with incomplete wash-out in subjects with solid tumors to determine the relative bioavailability of test formulation with lower dimethyl sulfoxide (DMSO) content as compared with standard reference formulation trametinib.

Approximately 18 subjects will be randomized to receive either a single dose of Treatment A (standard target DMSO content \[theoretical 11.3%\] formulation of GSK1120212B) or a single dose of Treatment B (lower DMSO Content \[approximately 9.5%\] formulation of GSK1120212B) followed by a 7 day incomplete wash-out period, then a single dose of the other treatment.

Administration of the dose under fasted conditions in Periods 1 and 2 will be only on Day 1 followed by 7 days of serial blood sampling for PK analysis of plasma trametinib. Safety assessments, including assessment of AEs, clinical laboratory (hematology and clinical chemistry) and vital signs, will be made throughout the study.

After a subject completes the study, he or she may be eligible to enter study MEK114375, an open-label rollover study of trametinib (no wash-out period or follow-up visit required) and continue receiving trametinib. For those subjects who wish to discontinue or complete the current study and choose not enter the rollover study, a follow-up visit should be performed within 21 days after receiving the last dose of study treatment.

A Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies

An Open-label, Randomized, 2-treatment, 2-period, 2-way Crossover, Single-dose Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies

Pharmacokinetic data will include corrected maximum plasma concentration (Cmax) of GSK1120212B. Comparison of Cmax will enable to determine the relative bioavailability of the test formulation with lower DMSO content (Treatment B) and the standard reference formulation (Treatment A). Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

Pharmacokinetic data will include corrected area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) of GSK1120212B. Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

Pharmacokinetic data will include corrected time of occurrence of Cmax (tmax) of GSK1120212B. Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

Pharmacokinetic data will include uncorrected Cmax of GSK1120212B.

Pharmacokinetic data will include uncorrected AUC(0-t), AUC(0-inf) and AUC from zero to 24 hrs AUC(0-24) of GSK1120212B.

Pharmacokinetic data will include uncorrected C0 of GSK1120212B in Period 2

Pharmacokinetic data will include t1/2 of GSK1120212B.

Safety data will include measurements of vital signs (blood pressure, pulse rate and temperature) at Baseline and end of the study.

Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry, coagulation and at Baseline and end of the study.

Safety data will include recording of number of subjects with AEs.

GlaxoSmithKline

Digestive System Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Micronutrients

Pembrolizumab

Docetaxel

Leucovorin

Fluorouracil

Irinotecan

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

(Closed for Enrollment)

Cohort 1:

* Week 1: selinexor 5 x 20-mg tablet daily;
* Week 2: selinexor 1 x 100-mg tablet daily

Cohort 2:

* Week 1: selinexor 1 x 100-mg tablet daily;
* Week 2: selinexor 5 x 20-mg tablet daily.

Cohort 3:

Patients with Moderate Hepatic Impairment with any Solid Tumors;

- Selinexor 2 x 20-mg tablet once weekly (QW).

Cohort 4:

Patients with Severe Hepatic Impairment with any Solid Tumors;

- Selinexor 2 x 20-mg tablet QW.

(Closed for Enrollment)

Selinexor 60 mg oral dose QW and docetaxel 75 mg/m\^2 intravenously (IV) once every 3 weeks (Non-small cell lung cancer \[NSCLC\] patients).

(Closed for Enrollment)

Selinexor 80 mg oral does QW and pembrolizumab 200 mg IV every 3 weeks (Colorectal cancer \[CRC\] Patients).

(Closed for Enrollment)

Cohort 1:

Selinexor 40 mg oral dose Days 1, 3, 15 and 18 in a 28-day cycle and FOLFIRI (irinotecan 180 mg/m\^2; leucovorin 400 mg/m\^2; 5- fluorouracil (5-FU) 400 mg/m\^2 bolus then 5-FU 2400 mg/m\^2 continuous over 46-48 hours; IV on Day 1 and 15 in a 28-day cycle) (CRC Patients).

Cohort 2:

Selinexor 80 mg oral dose Days 1 and 15 in a 28-day cycle and FOLFIRI (irinotecan 180 mg/m\^2; leucovorin 400 mg/m\^2; 5-FU 400 mg/m\^2 bolus then 5-FU 2400 mg/m\^2 continuous over 46-48 hours; IV on Day 1 and 15 in a 28-day cycle) (CRC Patients).

100-mg 2 formulations:

* 5 × 20-mg tablets (Tablet A)
* 1 × 100-mg tablet (Tablet B)

Selinexor 100 mg

FOLFIRI:

* Irinotecan 180 mg/m\^2
* Leucovorin 400 mg/m\^2
* 5-FU 400 mg/m\^2 bolus
* 5-FU 2400 mg/m\^2 IV

FOLFIRI

Selinexor 40 mg

Selinexor 80 mg

Selinexor 60 mg

Karyopharm Medical Information

Larissa Ryvo, MD

Julia Dudnik, MD

Valerya Seminesty, MD

Talia Shentzer Kutiel, MD

Nir Peled, MD

Aviad Zick, MD

Maya Gottfried, MD

Anton Ouryvaev, MD

Idit Peretz, MD

Ravit Geva, MD

Talia Golan, MD

This is a Phase 1/2, two-part, multi-arm, open-label study in patients with normal Hepatic Function (HF), with either Non-small cell lung cancer (NSCLC), who have had 1-2 prior lines of treatment, with 1 line containing a checkpoint Inhibitor (CPI); or patients with normal HF, with colorectal cancer (CRC) who have had 1-3 prior lines (KRAS wild-type \[WT\]) or 1-2 prior lines (mutant KRAS) of treatment with no CPI; or patients with impaired HF, with any solid tumor, who have had at least 1 prior line of treatment.

The study will comprise 2 treatment periods (monotherapy and combination therapy).

The purposes of this study, during Monotherapy period, are: (1) to determine the relative bioavailability of the 100 milligrams (mg) (Tablet B) and 20 mg (Tablet A) tablets of selinexor at 100 mg once weekly (QW) dose in patients with normal hepatic function; and (2) to assess the PK of selinexor after a single dose of 40 mg (2 × 20 mg), among patients with moderate and severe hepatic impairment, relative to 100 mg (5 × 20 mg), among patients with normal hepatic function; and, during the Combination therapy period, to assess the preliminary anti-tumor activity of selinexor in combination with docetaxel in patients with NSCLC and with pembrolizumab or folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) in patients with CRC.

Up to 120 patients will be enrolled, of which, 20 with normal HF will be able to continue from Monotherapy to Combination therapy and up to 106 patients with normal HF will receive combination therapy in total. Patients with impaired hepatic function can only participate in the Monotherapy part of the study.

Monotherapy Period:

For the Monotherapy Period of Study KCP-330-027, patients with normal hepatic function (n=20), will be allocated to one of two test formulation treatment arms, and will receive a cross-over once weekly oral dosing, with either 1x100 mg or 5x20 mg selinexor, for 2 weeks, and then will have the option to move on to the combination treatment part of the study. Patients with either moderately or severely impaired hepatic functions will be treated with 2x20 mg selinexor weekly (with an option to increase the dose every 3 weeks by 20 mg increments, up to 80 mg).

For the assessment of hepatic impairment, participants with any type of advanced or metastatic solid tumor who have moderate or severe hepatic impairment will be enrolled in Moderate Hepatic Impairment (MHI) (n=8) and Severe Hepatic Impairment (SHI) (n=6) arms, respectively and will be treated with 2 × 20 mg selinexor, weekly.

For Weeks 1 and 2, following an overnight fast of at least 10 hours, patients will be fed a standard low-fat meal 30 minutes prior to administration of once weekly selinexor. Patients should finish the meal in 30 minutes or less; however, selinexor dose should be administered 30 minutes after start of the meal.

Blood sampling for selinexor PK analyses will be collected ≤10 minutes (m) pre selinexor dose, and at 15m (±5m), 30m (±5m), 1 hour (h) (±5m), 1.5h (±5m), 2h (±10m), 3h (±10m), 4h (±10m), 5h (±10m), 6h (±10m), 8h (±20m), 10h (±20m; optional), 24h (±1h), 30h (±1h), and 48h (±2h) post selinexor dose. Practitioners must record the actual clock time for selinexor dose, and each sample drawn.

If a patient experiences emesis during the first 6 hours of the PK sampling, the PK results for that week will be excluded from the PK analysis dataset, and all testing timepoints must be re-collected during the following week (in this case, the same dosing formulation should be repeated on the following week, and other dosing formulation will be given the week after that).

Patients who will complete the Monotherapy Period will be reassessed for continuation to the Combination Therapy Period, as long as their Hepatic Function remains normal.

If a patient experiences significant toxicity related to selinexor and can't start the combination therapy immediately following monotherapy, dose interruption and weekly retesting are allowed for up to 21 days after the end of Monotherapy treatment visit. Patients requiring \>21 days to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for documented approval to continue to the Combination Therapy Period. Reassessment may be extended then and following Medical Monitor approval up to 28 days.

Combination Therapy Period:

In the combination treatment period of the study, patients with normal hepatic functions will be allocated to one of 3 arms (with Arm C divided into 2 cohorts): Arm A (n= up to 40): Patients with NSCLC who have had up to 2 lines of prior systemic treatment with 1 line containing a CPI will receive 60 mg selinexor weekly, in combination with docetaxel 75 milligrams per meter square (mg/m\^2) once every 3 weeks; Arm B (n= up to 40): Patients with CRC (KRAS WT) who have had up to 3 lines of prior systemic treatment or patients with CRC (KRAS mutant \[KRAS Mut\]) who have had up to 2 lines of prior systemic treatment, with no lines containing a checkpoint inhibitor (CPI) will receive 80 mg selinexor weekly, in combination with pembrolizumab 200 mg once every 3 weeks; Arm C (n\<=26): Patients with CRC (regardless of KRAS status) who have had up to 2 lines of prior systemic treatment (regardless of CPI use) will receive either: (Cohort 1) selinexor 40 mg on days 1, 3, 15 and 18 in 28-day cycle + FOLFIRI; or (Cohort 2) selinexor 80 mg on days 1 and 15 in 28-day cycle + FOLFIRI.

Combination Therapy Period Patients will receive combination treatment until progressive disease (PD) or intolerable toxicity.

During both study periods, safety will be assessed through continuous reporting of adverse events (AEs), treatment-emergent adverse events (TEAEs), regularly scheduled clinical laboratory tests (hematologic and chemical), and physical examinations.

Tumor assessment will be performed with either computed tomography (CT) or magnetic resonance imaging (MRI) (CT with contrast preferred; for each patient, the imaging method should remain the same throughout the study).

Following treatment, patients will come in for a safety visit (approximately 30 days after the last dose of combination therapy) and will be followed for up to 2 years after that. Patients who discontinued due to PD will be followed for survival, and patients who discontinued for reasons other than PD will have tumor assessments until PD or until the start of new anti-neoplastic therapy, after which they will be followed for survival.

Two part study (monotherapy period and combination therapy period).

Relative Bioavailability/Bioequivalence of Different Formulations of Selinexor, the Impact of Hepatic Impairment on Selinexor Pharmacokinetics, Tolerability and Antitumor Activity of Selinexor Combination Treatment

Open-Label, Phase 1/2 Study Evaluating the Relative Bioavailability/Bioequivalence of Different Formulations of Selinexor, the Impact of Hepatic Impairment on Selinexor Pharmacokinetics, and the Tolerability and Antitumor Activity of Selinexor Combination Treatment (SPRINT)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study in Healthy Subjects to Assess Bioavailability (Proportion of a Drug Which Enters the Circulation to Have an Active Effect) of Acalabrutinib Tablet and Protonpump Inhibitor Effect (Members of a Class of Medications That Inhibits in Gastric Acid Production) for Rabeprazole	NCT04564040	Mantle Cell Lym... COVID-19	Acalabrutinib T... Acalabrutinib T... Acalabrutinib T... Acalabrutinib T...	18 Years - 55 Years	AstraZeneca
Determination of the Relative Bioavailability of ARQ 197 Tablet Formulation With Capsule C Formulation as a Reference in Subjects With Advanced Solid Tumors	NCT01149720	Solid Tumors	Tivantinib (ARQ... Tivantinib (ARQ... Tivantinib (ARQ...	18 Years -	Daiichi Sankyo
A Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies	NCT01725100	Cancer	GSK1120212B (St... GSK1120212B (Lo...	18 Years -	GlaxoSmithKline
Relative Bioavailability/Bioequivalence of Different Formulations of Selinexor, the Impact of Hepatic Impairment on Selinexor Pharmacokinetics, Tolerability and Antitumor Activity of Selinexor Combination Treatment	NCT04256707	Non-Small Cell ... Colorectal Canc... Other Solid Tum...	Selinexor 100 m... Docetaxel Pembrolizumab FOLFIRI Selinexor 40 mg Selinexor 80 mg Selinexor 60 mg	18 Years -	Karyopharm Therapeutics Inc
A Study in Healthy Subjects to Assess Bioavailability (Proportion of a Drug Which Enters the Circulation to Have an Active Effect) of Acalabrutinib Tablet and Protonpump Inhibitor Effect (Members of a Class of Medications That Inhibits in Gastric Acid Production) for Rabeprazole	NCT04564040	Mantle Cell Lym... COVID-19	Acalabrutinib T... Acalabrutinib T... Acalabrutinib T... Acalabrutinib T...	18 Years - 55 Years	AstraZeneca

Spots Global Cancer Trial Database for relative bioavailability