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A Study of NDI 1150-101 in Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05128487
Recruitment Status : Recruiting
First Posted : November 22, 2021
Last Update Posted : May 20, 2022
Sponsor:
Information provided by (Responsible Party):
Nimbus Therapeutics ( Nimbus Saturn, Inc. )

Brief Summary:
This study is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) and to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of NDI-101150 given as monotherapy or in combination with pembrolizumab in adult male and female patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: NDI-101150 Drug: Pembrolizumab Phase 1 Phase 2

Detailed Description:

This is a multicenter, open-label, two-part, first-in-human, Phase 1/2 study.

In this 2 parts study, eligible patients will be enrolled in Part 1 (Dose Escalation Phase: designed to evaluate the safety and tolerability of NDI-101150 as monotherapy and in combination with pembrolizumab) and Part 2 (Dose Expansion Phase: designed to evaluate the safety and efficacy of NDI-101150 as monotherapy and in combination with pembrolizumab in disease-specific (gastric and gastroesophageal junction [GEJ] cancer) dose expansion cohorts).

Each part of the study will consist of 3 phases:

  • A Screening Phase of up to 28 days during which patient eligibility will be reviewed and approved by the Sponsor.
  • Treatment Phase that will extend from Cycle 1 Day 1 until progression of disease (PD), unacceptable toxicity, withdrawal of consent, start of a new systemic anticancer treatment, discontinuation of the patient by the Investigator, or termination of the study by the Sponsor (and will include Safety Follow-up Visit 30 days [+3 days] after the last dose of investigational medicinal product).
  • Post treatment Follow-up Phase which will continue until lost to follow-up, withdrawal of consent, or the End of the Study (whichever comes first).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of NDI-101150 Administered as Monotherapy or in Combination With Pembrolizumab in Patients With Solid Tumors
Actual Study Start Date : November 5, 2021
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NDI-101150 (Monotherapy)
Patients in escalation and expansion, will receive NDI-101150 capsules orally once daily continuously in 4-week cycles (28 days).
Drug: NDI-101150
NDI-101150 capsules

Experimental: NDI-101150-Pembrolizumab (Combination therapy)
Patients in escalation and expansion phase, will receive NDI-101150 capsules orally once daily continuously in 3-week cycles (21 days), along with pembrolizumab via intravenous (IV) infusion at a dose of 200 mg every 3 weeks.
Drug: NDI-101150
NDI-101150 capsules

Drug: Pembrolizumab
Pembrolizumab IV infusion




Primary Outcome Measures :
  1. Part 1: Frequency of dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (28 days) ]
    Frequency of DLTs associated with NDI-101150 administration alone (escalation monotherapy cohorts) in patients with advanced solid tumors will be determined to evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.

  2. Part 1: Frequency of dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 and Cycle 2 (each cycle is 21 days in length) ]
    Frequency of DLTs associated with NDI-101150 administration alone (escalation monotherapy cohorts) in patients with advanced solid tumors will be determined to evaluate the MTD and RP2D of NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.

  3. Part 2: Objective response rate (ORR) [ Time Frame: Up to approximately 34 months ]
    Preliminary antitumor activity of NDI-101150 monotherapy and in combination with pembrolizumab in patients with specific solid tumors (gastric and GEJ cancer). An ORR is defined as percentage of patients with a best overall response of complete response (CR) or partial response (PR), according to o Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 as assessed by the Investigator.


Secondary Outcome Measures :
  1. Part 1 and Part 2: Number of patients with adverse events (AEs) and Serious adverse events (SAEs) [ Time Frame: From Screening (Day -28 to Day -1) until safety follow-up (>30 days after last dose) [Assessed up to 37 months] ]
    Safety and tolerability of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be characterized.

  2. Part 1 and Part 2: Maximum plasma concentration (Cmax) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    Cmax of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  3. Part 1 and Part 2: Time to maximum plasma concentration (tmax) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET (Cycle length is 28 days for monotherapy and 21 days for combination therapy) [Assessed up to 37 months] ]
    tmax of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  4. Part 1 and Part 2: Elimination half-life (t1/2) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    t1/2 of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  5. Part 1 and Part 2: Volume of distribution (Vz/F) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    Vz/F of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  6. Part 1 and Part 2: Clearance (CL/F) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    CL/F of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  7. Part 1 and Part 2: Area under the concentration-time curve from time zero to the last observable concentration (AUC0-t) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    AUC0-t of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  8. Part 1: Area under the concentration-time curve in the dosing interval (AUC0-24) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    AUC0-24 of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors will be determined.

  9. Part 1 and Part 2: Area under the concentration-time curve extrapolated to infinity (AUC0-∞) of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    AUC0-∞ of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  10. Part 1 and Part 2: Accumulation index based on Cmax of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    Accumulation index of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  11. Part 1 and Part 2: Accumulation index based on AUC of NDI-101150 [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (pre-dose and post-dose), at Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy) and at EOT/ET [Cycle length is 28 days for monotherapy and 21 days for combination therapy] [Assessed up to 37 months] ]
    Accumulation index of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be determined.

  12. Part 1: Objective response rate (ORR) [ Time Frame: Assessed up to 37 months ]
    Preliminary antitumor activity of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors will be evaluated. An ORR is defined as percentage of patients with a best overall response of CR or PR, according to RECIST v1.1 as assessed by the Investigator.

  13. Part 1 and Part 2: Progression-free survival (PFS) [ Time Frame: From first dose until confirmed progression of disease (PD) or death (Assessed up to 37 months) ]
    Preliminary antitumor activity of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be evaluated. PFS defined as the time from first dose to confirmed progression of disease (PD) or death, according to RECIST v1.1 as assessed by the Investigator.

  14. Part 1 and Part 2: Duration of response (DOR) [ Time Frame: Time from first response until confirmed PD (Assessed up to 37 months) ]
    Preliminary antitumor activity of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and with specific solid tumors (gastric and GEJ cancer) will be evaluated. DOR is defined as the time from the date of first response to the date of confirmed PD, according to RECIST v1.1 as assessed by the Investigator.

  15. Part 1 and Part 2: Time to response (TTR) [ Time Frame: Time from first dose until first response (Assessed up to 37 months) ]
    Preliminary antitumor activity of NDI-101150 monotherapy and in combination with pembrolizumab in patients with advanced solid tumors and specific solid tumors (gastric and GEJ cancer) will be evaluated. TTR is defined as the time from first dose to date of first response, according to RECIST v1.1 as assessed by the Investigator.

  16. Part 2: Overall survival [ Time Frame: Assessed up to 37 months ]
    Additional antitumor activity of NDI-101150 monotherapy and in combination with pembrolizumab in patients with specific solid tumors (gastric and GEJ cancer) will be evaluated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Life expectancy of ≥ 12 weeks
  • Measurable or non-measurable disease for Part 1; measurable disease using RECIST v1.1 is required for Part 2
  • Recovered from prior therapy to Grade ≤ 1 or return to baseline status (except for alopecia)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients with adequate bone marrow function
  • Last dose of previous anticancer therapy ≥ 4 weeks prior to first dose of NDI-101150; includes prior anti-PD-1 or anti-PD-L1 therapy, other anticancer therapy, radiotherapy, or surgical intervention
  • For Part 2, willing to consent to required tumor biopsy(ies)
  • For Part 1 Only (Dose Escalation, Monotherapy and Combination Therapy): Histologically or cytologically confirmed advanced or metastatic solid tumors for whom no standard therapies are available or refractory to standard therapy
  • For Part 2 (Dose Expansion, Monotherapy and Combination Therapy): Histologically or cytologically confirmed advanced or metastatic gastric or GEJ adenocarcinoma for which no standard therapy is available or are refractory to standard therapy

Exclusion Criteria:

  • Previous solid organ or hematopoietic cell transplant
  • Central nervous system (CNS) malignant disease not previously treated, active leptomeningeal disease, uncontrolled symptomatic CNS involvement, or CNS malignant disease requiring steroid or other therapeutic intervention
  • Prior anticancer treatment
  • Clinically significant cardiovascular disease
  • History of severe hypersensitivity reaction to treatment with monoclonal antibody(ies) (for combination therapy cohorts only)
  • History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of history of pneumonitis on chest computed tomography scan in the last 6 months
  • Known additional malignancy that is active and/or progressive requiring treatment
  • Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical or psychiatric illness or abnormal laboratory finding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05128487


Contacts
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Contact: Study Coordinator 8579992009 clinical@nimbustx.com

Locations
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United States, Arizona
Honor Health Research Institute Not yet recruiting
Scottsdale, Arizona, United States, 85258
United States, District of Columbia
Georgetown University Not yet recruiting
Washington, District of Columbia, United States, 20007-2113
United States, Florida
Ocala Oncology Center Not yet recruiting
Ocala, Florida, United States, 34474
United States, New Jersey
Hackensack University Recruiting
Hackensack, New Jersey, United States, 07601
United States, Texas
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Nimbus Saturn, Inc.
Investigators
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Study Director: Dan Rudin, MD Nimbus Saturn
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Responsible Party: Nimbus Saturn, Inc.
ClinicalTrials.gov Identifier: NCT05128487    
Other Study ID Numbers: 1150-101
First Posted: November 22, 2021    Key Record Dates
Last Update Posted: May 20, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nimbus Therapeutics ( Nimbus Saturn, Inc. ):
Dose escalation phase
Dose expansion phase
Hematopoietic progenitor kinase 1
NDI-101150
First-in-human
Maximum tolerated dose
Recommended Phase 2 dose
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents