Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies

NCT ID: NCT02419495

Last Updated: 2025-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

221 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-26

Study Completion Date

2024-09-16

Brief Summary

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This phase Ib trial studies the side effects and best dose of selinexor when given together with several different standard chemotherapy or immunotherapy regimens in treating patients with malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Selinexor may stop the growth of cancer cells by blocking enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Studying selinexor with different standard chemotherapy or immunotherapy regimens may help doctors learn the side effects and best dose of selinexor that can be given with different types of treatments in one study.

Detailed Description

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PRIMARY OBJECTIVE:

I. To establish the safety and tolerability of selinexor when given in combination with standard chemotherapy or immunotherapy regimens.

SECONDARY OBJECTIVE:

I. To determine disease control rate, objective tumor response rate, and progression free survival of selinexor administered with standard chemotherapy or immunotherapy treatments.

EXPLORATORY OBJECTIVES:

I. To determine the correlation of translational biomarkers. II. To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy.

III. To assess the efficacy of olanzapine as incorporated in the National Comprehensive Cancer Network (NCCN) guidelines for the management of chemotherapy-induced nausea and cachexia.

OUTLINE: This is a dose-escalation study of selinexor. Patients are assigned to 1 of 15 treatment arms.

ARM A: Patients receive selinexor orally (PO) on days 1, 8, and 15 and carboplatin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM B: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles, of combination treatment, patients can continue single agent selinexor until disease progression.

ARM C: Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

ARM D: Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM E: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending on cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM F: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM G: Patients receive selinexor PO on days 1, 8, and 15 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM H: Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil continuous IV and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM I: Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM J: Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM K: Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (ARM CLOSED)

ARM L: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM M: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARMS N AND O: Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM P: Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients may continue to receive selinexor and chemotherapy after confirmed progressive disease in the absence of clinical deterioration and if the investigator considers that the patient continues to receive benefit from the treatment.

After completion of study treatment, patients are followed up every 12 weeks for 1 year.

Conditions

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Advanced Malignant Solid Neoplasm Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Fallopian Tube Carcinoma Metastatic Lung Non-Small Cell Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Melanoma Metastatic Renal Cell Carcinoma Ovarian Carcinoma Pathologic Stage III Cutaneous Melanoma AJCC v8 Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IIID Cutaneous Melanoma AJCC v8 Pathologic Stage IV Cutaneous Melanoma AJCC v8 Primary Peritoneal Carcinoma Stage III Lung Cancer AJCC v8 Stage III Renal Cell Cancer AJCC v8 Stage IIIA Lung Cancer AJCC v8 Stage IIIB Lung Cancer AJCC v8 Stage IIIC Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IV Renal Cell Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Triple-Negative Breast Carcinoma Unresectable Lung Non-Small Cell Carcinoma Unresectable Melanoma Unresectable Renal Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (selinexor, carboplatin) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm B (selinexor, paclitaxel)

Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles of combination treatment, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm C (selinexor, eribulin)

Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Eribulin

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending con cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Given IV

Paclitaxel

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Given IV

Pemetrexed

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, and 15 and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Given PO

Topotecan

Intervention Type DRUG

Given IV

Arm H (selinexor, FOLFIRI) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV continuously over 48 hours and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.

Group Type EXPERIMENTAL

Capecitabine

Intervention Type DRUG

Given PO

Oxaliplatin

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm K (selinexor, olaparib) (ARM CLOSED)

Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Olaparib

Intervention Type DRUG

Given PO

Selinexor

Intervention Type DRUG

Given PO

Arm L (selinexor, pembrolizumab)

Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm M (selinexor, nivolumab

Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arm P (selinexor, nivolumab, ipilimumab)

Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Selinexor

Intervention Type DRUG

Given PO

Arms N and O (selinexor, nivolumab, ipilimumab)

Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Selinexor

Intervention Type DRUG

Given PO

Interventions

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Capecitabine

Given PO

Intervention Type DRUG

Carboplatin

Given IV

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Doxorubicin

Given IV

Intervention Type DRUG

Eribulin

Given IV

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Ipilimumab

Given IV

Intervention Type BIOLOGICAL

Irinotecan Hydrochloride

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IV

Intervention Type DRUG

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Olaparib

Given PO

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Paclitaxel

Given IV

Intervention Type DRUG

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Pemetrexed

Given IV

Intervention Type DRUG

Selinexor

Given PO

Intervention Type DRUG

Topotecan

Given IV

Intervention Type DRUG

Other Intervention Names

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Ro 09-1978/000 Xeloda Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Adriablastin Hydroxydaunomycin Hydroxyl Daunorubicin Hydroxyldaunorubicin ER-086526 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 Irinomedac Irinotecan Hydrochloride Trihydrate Irinotecan Monohydrochloride Trihydrate U-101440E Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo AZD 2281 AZD-2281 AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Keytruda Lambrolizumab MK-3475 SCH 900475 MTA Multitargeted Antifolate Pemfexy ATG-010 CRM1 Nuclear Export Inhibitor KPT-330 KPT-330 Selective Inhibitor of Nuclear Export KPT-330 SINE KPT-330 Xpovio Hycamptamine Topotecan Lactone

Eligibility Criteria

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Inclusion Criteria

* Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment; patients in Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) that have Food and Drug Administration (FDA)-approved indications for nivolumab, ipilimumab, and pembrolizumab do not have to fail first line nivolumab, ipilimumab, or pembrolizumab, and these patients may be treatment naïve if they have disease where pembrolizumab or nivolumab are FDA approved for the first-line setting
* For all arms except Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) patients must have failed prior standard curative chemotherapy for their disease; subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
* Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* The patient must be recovered from a prior major surgery; the major surgery must be performed at least 4 weeks prior to consent date
* Platelets \>= 125 x 10\^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P \[nivolumab and ipilimumab\] and expansion cohorts for all arms, platelets \>= 100 x 10\^9/L)
* Hemoglobin \>= 10 g/dL (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P \[nivolumab and ipilimumab\] and expansion cohorts for all arms, hemoglobin \>= 9 g/dL)
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P \[nivolumab and ipilimumab\], ANC \>= 1.0 x 10\^9/L)
* Transfusions and growth factors are allowed
* Alanine transaminase (alanine aminotransferase \[ALT\]) =\< 2 x upper normal limit (ULN) (in the expansion cohort, patients with known liver involvement may have ALT =\< 5 x ULN); aspartate aminotransferase (AST) =\< 2 x ULN (in the expansion cohort, patients with known liver involvement may have AST =\< 5 x ULN)
* Alkaline phosphatase \< 4 x ULN
* Total bilirubin =\< 2 x ULN (in the expansion cohort, patients with Gilbert's syndrome \[hereditary indirect hyperbilirubinemia\] who must have a total bilirubin of =\< 3 x ULN)
* Renal function defined as a calculated or measured glomerular filtration rate (GFR) \>= 30 mL/min. For patients with renal cell carcinoma (RCC), the GFR may be defined as \>= 25 mL/min
* Life expectancy of at least 12 weeks
* Able to swallow and retain oral medication
* Patients must give informed consent according to the rules and regulations of the individual participating sites
* Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during/after 3 months post dose; a woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant; this includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices
* For the Arm B (paclitaxel) expansion cohort, patients must have ovarian carcinoma, fallopian tube, or peritonea carcinoma
* For Arm C (eribulin) expansion cohort, patients must have triple negative breast cancer (eribulin naive)
* For Arm M (nivolumab) expansion phase, patients must have biopsiable disease
* For the Arm N (nivolumab and ipilimumab), patients must have metastatic or unresectable renal cell carcinoma (RCC)
* For the Arm O (nivolumab and ipilimumab) escalation and expansion Cohort O-1, patients must have metastatic or unresectable melanoma
* For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must have metastatic or advanced solid tumors (non-melanoma, non-renal cell carcinoma, or non- non-small cell lung carcinoma)
* For the Arm P (nivolumab and ipilimumab), patients must have metastatic or unresectable non-small cell lung carcinoma (NSCLC)

Exclusion Criteria

* Evidence of complete or partial bowel obstruction
* Patients with primary central nervous system (CNS) tumor or CNS tumor involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is:

* \> 4 weeks from prior therapy completion (including radiation and/or surgery)
* Clinically stable with respect to the CNS tumor at the time of study entry
* Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement
* Not receiving anti-convulsive medications (that were started for brain metastases)
* Need of total parenteral nutrition
* Prior treatment with an agent targeting the exportin
* Allergic to selinexor or any of the chemotherapy intended to receive
* Pregnancy or lactation
* Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) =\< 3 weeks prior to study drug administration date
* Chemotherapy, or immunotherapy or any other systemic anticancer therapy =\< 3 weeks prior to study drug administration date; patients receiving anti-PD-1 treatment, and continue to receiving this treatment in combination with selinexor (Arms L, M, N, O, and P), can start receiving the selinexor and anti-PD-1 combination without washout of the prior anti-PD-1 antibody
* Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated)
* Major surgery within four weeks before consent date
* Unstable cardiovascular function: symptomatic ischemia (chest pain of cardiac origin), or uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular \[AV\] block or asymptomatic left anterior fascicular block \[LAFB\]/right bundle branch block \[RBBB\] will not be excluded), or congestive heart failure (CHF) of New York Heart Association (NYHA) class \>= 3, or myocardial infarction (MI) within 3 months of consent date
* Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose; active infection with concurrent treatment is acceptable only if the patient is clinically stable
* Significantly diseased (as determined by the principal investigator \[PI\] or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
* Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date
* Concurrent therapy with approved or investigational anticancer therapeutics
* Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
* Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception; highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 3 months after the end of study treatment; women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months)
* For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects with an active, known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or other form of immunosuppressive therapy within 7 days before the first dose of study treatment; use of inhaled or topical steroids or systemic corticosteroids =\< 10 mg is permitted; in addition, physiologic steroid replacement with hydrocortisone is allowed
* For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), history of a prior grade 3 or 4 immune-related adverse event (irAE) or any grade ocular irAE from prior immunotherapy
* For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must not have melanoma, RCC, or NSCLC
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aung Naing, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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MD Anderson in The Woodlands

Conroe, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

MD Anderson West Houston

Houston, Texas, United States

Site Status

MD Anderson League City

League City, Texas, United States

Site Status

MD Anderson in Sugar Land

Sugar Land, Texas, United States

Site Status

Countries

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United States

References

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Alhalabi O, Gouda MA, Milton DR, Momin HA, Yilmaz B, Stephen B, Ejezie CL, Moyers JT, Gurses SA, How J, Fu S, Rodon J, Hong DS, Piha-Paul SA, Subbiah V, Elena Dumbrava E, Karp DD, Janku F, Meric-Bernstam F, Tannir NM, Naing A. A Phase IB Trial of Selinexor in Combination With Immune Checkpoint Blockade in Patients With Advanced Renal Cell Carcinoma. Cancer Med. 2025 Feb;14(4):e70280. doi: 10.1002/cam4.70280.

Reference Type DERIVED
PMID: 39945382 (View on PubMed)

Gouda MA, Zarifa A, Yang Y, Stephen B, Gurses SA, Sprenger A, Tian Y, Derbala MH, Oliva IG, Meric-Bernstam F, Patel SP. Selinexor (KPT-330) in Combination with Immune Checkpoint Inhibition in Uveal Melanoma: A Phase 1B Trial. J Immunother Precis Oncol. 2025 Jan 15;8(1):82-88. doi: 10.36401/JIPO-24-10. eCollection 2025 Feb.

Reference Type DERIVED
PMID: 39816915 (View on PubMed)

Altan M, Tu J, Milton DR, Yilmaz B, Tian Y, Fossella FV, Mott FE, Blumenschein GR, Stephen B, Karp DD, Meric-Bernstam F, Heymach JV, Naing A. Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non-small cell lung cancer. Cancer. 2023 Sep 1;129(17):2685-2693. doi: 10.1002/cncr.34820. Epub 2023 May 2.

Reference Type DERIVED
PMID: 37129197 (View on PubMed)

Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Fu S, Subbiah V, Hong DS, Yap TA, Shah J, Milton DR, McQuinn L, Gong J, Tran Y, Carter BW, Colen R, Meric-Bernstam F, Naing A. Selinexor in combination with standard chemotherapy in patients with advanced or metastatic solid tumors. Exp Hematol Oncol. 2021 Dec 29;10(1):59. doi: 10.1186/s40164-021-00251-0.

Reference Type DERIVED
PMID: 34965890 (View on PubMed)

Thein KZ, Karp DD, Tsimberidou A, Gong J, Sulovic S, Shah J, Milton DR, Hong DS, Janku F, McQuinn L, Stephen BA, Colen R, Carter BW, Yap TA, Piha-Paul SA, Fu S, Meric-Bernstam F, Naing A. Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. Invest New Drugs. 2022 Apr;40(2):290-299. doi: 10.1007/s10637-021-01188-1. Epub 2021 Sep 25.

Reference Type DERIVED
PMID: 34562230 (View on PubMed)

Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Zarifa A, Shah J, Milton DR, Bean S, McQuinn L, Gong J, Colen R, Carter BW, Subbiah V, Ogbonna DC, Pant S, Meric-Bernstam F, Naing A. Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study. Invest New Drugs. 2021 Oct;39(5):1357-1365. doi: 10.1007/s10637-021-01119-0. Epub 2021 Apr 28.

Reference Type DERIVED
PMID: 33909232 (View on PubMed)

Related Links

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http://www.mdanderson.org

M D Anderson Cancer Center

Other Identifiers

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NCI-2015-00693

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-0640

Identifier Type: OTHER

Identifier Source: secondary_id

2014-0640

Identifier Type: -

Identifier Source: org_study_id

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