Non-small Cell Lung CancerPhase 1/2NCT04263090
Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment
A Phase 1/2 study testing Rigosertib and Nivolumab in people with Non-small Cell Lung Cancer and Adenocarcinoma, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
A Phase1/2a Study of Rigosertib plus Nivolumab in Stage IV Lung Adenocarcinoma Patients with KRAS Mutation who Progressed on First-Line Treatment Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer, Adenocarcinoma, Stage IV
- What is being tested?
- Rigosertib and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2020to 20 Dec 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent for the trial.
- Be at least 18 years of age on the day of signing informed consent.
- Have a histologically or cytologically confirmed diagnosis of Stage IV metastatic lung adenocarcinoma (AJCC version 8) with mutation analysis by next generation sequencing (NGS) confirming KRAS mutation either at time of diagnosis or at progression on first line treatment.
- Have progressed on or intolerant of standard of care first-line treatment with anti-programmed death-ligand 1 (PD1) checkpoint inhibitor monotherapy or anti-PD1 checkpoint inhibitor in combination with platinum doublet chemotherapy for Stage IV metastatic lung adenocarcinoma. The last cycle of first-line treatment must occur at least 28 days prior to administration of trial drugs (i.e., washout period)
- Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesion.
- Have a life expectancy of at least 3 months.
Show all 12Show fewer
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- Have adequate organ function as indicated by the following laboratory values in Table 1. Specimens must be collected within 14 days prior to the start of trial.
- Patient must be willing and able to provide blood samples (12 green tops tubes, roughly 100mL) at the time points indicated in the Study Calendar.
- Patient must be willing and able to have core needle biopsies (Goal 4-8 biopsies, final number to be determined by the surgeon and radiologist performing the procedure as safe) of tumor prior to initiation of study drug, and at time points indicated in the Study Calendar.
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and following completion of therapy for 5 months if female and 7 months if male.
- Female subjects of child-bearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Who cannot join
- Patients may not be receiving any other investigational agents. If received as part of first line treatment, last administration of previous investigational agent must be greater than 4 weeks prior to administration of study drug combination.
- Patients must not be pregnant or nursing due to the potential for congenital abnormalities or harm to nursing infants.
- Tumor harbors an epidermal growth factor receptor (EGFR) sensitizing (activating) mutation or an anaplastic lymphoma kinase (ALK) translocation. All other co-mutations will be allowed.
- Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are without evidence of progression for at least 4 weeks by repeat radiological imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study drug.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
- Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.
Show all 14Show fewer
- Has a known additional malignancy that is progressing and/or required active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical or anal cancer, prostate cancer on stable dose of hormonal therapy without rising prostate-specific antigen (PSA), and breast cancer whom have been treated with curative intent, who may be on hormonal therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with <350 cluster of differentiation 4 (CD4+) T cells/microliter in the peripheral blood. No HIV testing is required.
- History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
- Receipt of a live vaccine within 30 days of planned start of study medication
- History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immunosuppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either psychiatric or physical (e.g. infectious disease) illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Phase1/2a Study of Rigosertib Plus Nivolumab in Stage IV Lung Adenocarcinoma Patients With KRAS Mutation Who Progressed on First-Line Treatment
A Phase1/2a Study of Rigosertib plus Nivolumab in Stage IV Lung Adenocarcinoma Patients with KRAS Mutation who Progressed on First-Line Treatment
Read the detailed description
This is an open-label, dose-escalating Phase I study followed by a Phase 2a dose-expansion phase to study the combination of Rigosertib and Nivolumab in metastatic Kirsten rat sarcoma positive (KRAS+) lung adenocarcinoma patients who have progressed on standard first line treatment. Study patients will have satisfied the inclusion/exclusion criteria enumerated in this protocol. The Phase I dose escalation plan will start with an accelerated titration design (ATD) using single patient cohorts until grade 2 toxicity is experienced. At that point, the ATD will be terminated and the dose escalation will enter a standard 3+3 design based on dose-limiting toxicities (DLT). The MTD (Phase 1 primary endpoint) is defined as the highest dose for which at most 1 patient out of 6 experiences a DLT.
Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg in the morning (qAM), 280mg in the evening (qPM); dose D3: 560mg twice daily; taken by mouth for 21 consecutive days of the 28 day cycle), based on previous dose escalation studies in other malignancies, while Nivolumab dose will be fixed at the standard dose (240mg every 2 weeks, given intravenously).
Once the MTD is determined, an additional planned 12 patients will be enrolled in the expansion phase to further study toxicity and to determine preliminary efficacy endpoints including ORR (phase 2a primary endpoint), PFS, and OS (secondary endpoints) of the combination.
- Conditions
- Non-small Cell Lung Cancer, Adenocarcinoma, Stage IV
- Being tested
- Rigosertib, Nivolumab
- Keywords
- KRAS, Metastatic, Rigosertib, Immunotherapy, Nivolumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Adenocarcinoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RigosertibDrug
Rigosertib will be dosed twice a day for 21 consecutive days, followed by 7 days off treatment (each cycle duration: 28 days). Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg qAM, 280mg qPM; dose D3: 560mg twice daily).
NivolumabDrug
Nivolumab will be dosed once ever 2 weeks (twice per 28-day cycle; standard fixed dose of 240mg).
| Study group | Role | What they receive |
|---|---|---|
| Rigosertib + Nivolumab | Experimental | Rigosertib + Nivolumab in metastatic KRAS+ lung adenocarcinoma patients Receives: Drug: Rigosertib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Tolerated Dose (MTD)
MTD is defined as the highest dose for which at most 1 patient out of 6 experiences a dose-limiting toxicity (DLT)
Measured: DLTs will be evaluated at the end of Cycle 1 (each cycle is 28 days)
Overall Response Rate (ORR)
ORR is defined as achieving an objective response of either complete response or partial response
Measured: 2 years
Secondary outcomes (2)
Progression Free Survival (PFS)
Phase 2: PFS is defined as the duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier.
Measured: 2 years
Overall Survival (OS) at MTD
Phase 2: OS at MTD is defined as the time from the first dose of study treatment to the date of death (whatever the cause).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start29 Jun 2020
- Primary completion20 Dec 2023
- Study completion20 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Dose-escalating Phase I study followed by a Phase 2a dose-expansion phase. Rigosertib escalation will occur with three dose levels: Dose D1: 280mg twice daily, Dose D2: 560mg qAM, 280mg qPM, Dose D3: 560mg twice daily. Nivolumab will be dosed at the standard fixed dose of 240mg.
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Traws Pharma, Inc.
- Responsible party
- Principal investigator, Rajwanth Veluswamy, Icahn School of Medicine at Mount Sinai
- Investigators
- Rajwanth Veluswamy, MD, MSCR, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04263090
- Sponsor's protocol ID
- GCO 19-2243
- Status last verified
- May 2024
- First submitted
- 5 Feb 2020
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase1/2a Study of Rigosertib Plus Nivolumab in Stage IV Lung Adenocarcinoma Patients With KRAS Mutation Who Progressed on First-Line Treatment
- ClinicalTrials.gov ID
- NCT04263090
- Acronym / sponsor ID
- GCO 19-2243
- Conditions
- Non-small Cell Lung Cancer, Adenocarcinoma, Stage IV
- Keywords
- KRAS, Metastatic, Rigosertib, Immunotherapy, Nivolumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Traws Pharma, Inc.
- Study start
- 29 Jun 2020 (actual)
- Primary completion
- 20 Dec 2023 (actual)
- Study completion
- 20 Dec 2023 (actual)
- First posted
- 10 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase1/2a Study of Rigosertib plus Nivolumab in Stage IV Lung Adenocarcinoma Patients with KRAS Mutation who Progressed on First-Line Treatment
Detailed description
This is an open-label, dose-escalating Phase I study followed by a Phase 2a dose-expansion phase to study the combination of Rigosertib and Nivolumab in metastatic Kirsten rat sarcoma positive (KRAS+) lung adenocarcinoma patients who have progressed on standard first line treatment. Study patients will have satisfied the inclusion/exclusion criteria enumerated in this protocol. The Phase I dose escalation plan will start with an accelerated titration design (ATD) using single patient cohorts until grade 2 toxicity is experienced. At that point, the ATD will be terminated and the dose escalation will enter a standard 3+3 design based on dose-limiting toxicities (DLT). The MTD (Phase 1 primary endpoint) is defined as the highest dose for which at most 1 patient out of 6 experiences a DLT.
Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg in the morning (qAM), 280mg in the evening (qPM); dose D3: 560mg twice daily; taken by mouth for 21 consecutive days of the 28 day cycle), based on previous dose escalation studies in other malignancies, while Nivolumab dose will be fixed at the standard dose (240mg every 2 weeks, given intravenously).
Once the MTD is determined, an additional planned 12 patients will be enrolled in the expansion phase to further study toxicity and to determine preliminary efficacy endpoints including ORR (phase 2a primary endpoint), PFS, and OS (secondary endpoints) of the combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose-escalating Phase I study followed by a Phase 2a dose-expansion phase. Rigosertib escalation will occur with three dose levels: Dose D1: 280mg twice daily, Dose D2: 560mg qAM, 280mg qPM, Dose D3: 560mg twice daily. Nivolumab will be dosed at the standard fixed dose of 240mg.
| Arm | Type | Receives |
|---|---|---|
| Rigosertib + Nivolumab | Experimental | Drug: Rigosertib, Drug: NivolumabRigosertib + Nivolumab in metastatic KRAS+ lung adenocarcinoma patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be willing and able to provide written informed consent for the trial.
- Be at least 18 years of age on the day of signing informed consent.
- Have a histologically or cytologically confirmed diagnosis of Stage IV metastatic lung adenocarcinoma (AJCC version 8) with mutation analysis by next generation sequencing (NGS) confirming KRAS mutation either at time of diagnosis or at progression on first line treatment.
- Have progressed on or intolerant of standard of care first-line treatment with anti-programmed death-ligand 1 (PD1) checkpoint inhibitor monotherapy or anti-PD1 checkpoint inhibitor in combination with platinum doublet chemotherapy for Stage IV metastatic lung adenocarcinoma. The last cycle of first-line treatment must occur at least 28 days prior to administration of trial drugs (i.e., washout period)
- Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesion.
Key exclusion criteria (14 listed)
- Patients may not be receiving any other investigational agents. If received as part of first line treatment, last administration of previous investigational agent must be greater than 4 weeks prior to administration of study drug combination.
- Patients must not be pregnant or nursing due to the potential for congenital abnormalities or harm to nursing infants.
- Tumor harbors an epidermal growth factor receptor (EGFR) sensitizing (activating) mutation or an anaplastic lymphoma kinase (ALK) translocation. All other co-mutations will be allowed.
- Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are without evidence of progression for at least 4 weeks by repeat radiological imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study drug.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RigosertibRigosertib will be dosed twice a day for 21 consecutive days, followed by 7 days off treatment (each cycle duration: 28 days). Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg qAM, 280mg qPM; dose D3: 560mg twice daily). | Drug | Rigosertib + Nivolumab |
| NivolumabNivolumab will be dosed once ever 2 weeks (twice per 28-day cycle; standard fixed dose of 240mg). | Drug | Rigosertib + Nivolumab |
Primary outcome
Maximal Tolerated Dose (MTD)
Time frame: DLTs will be evaluated at the end of Cycle 1 (each cycle is 28 days)
MTD is defined as the highest dose for which at most 1 patient out of 6 experiences a dose-limiting toxicity (DLT)
Overall Response Rate (ORR)
Time frame: 2 years
ORR is defined as achieving an objective response of either complete response or partial response
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: 2 years
Overall Survival (OS) at MTD
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
Related trials for Non-small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajwanth Veluswamy, MD, MSCR principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rigosertib and Nivolumab in people with Non-small Cell Lung Cancer and Adenocarcinoma, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Tolerated Dose (MTD) (time frame: DLTs will be evaluated at the end of Cycle 1 (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2024.