Study Using a Drug-device Combination Product to Determine Safety, Tolerability and Antitumor Activity for Patients With Advanced, Non-small Cell Lung Cancer

Browse trials for

• Carcinoma, Non-Small-Cell Lung 6,488
• Lung Neoplasms 7,243

Keywords

• Lung Cancer
• Non-small cell

Carcinoma, Non-Small-Cell Lung

6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.

This study's planned enrollment of 100 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Lead sponsor

This is the only study on the registry with Nob Hill Therapeutics, Inc. as lead sponsor.

Study arms

• Experimental
  Dose Escalation

  Participants receive NHT102 via inhalation once daily on Days 1-5 and Days 15-19 of each 28 day cycle. Up to five dose levels (7 mg to 42 mg target lung dose \[TLD\] per treatment day) are evaluated using a standard 3+3 design to determine dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Additional intermediate dose level cohorts may be added at the recommendation of the Safety Review Committee (SRC). Interventions: NHT102 (5-AZA dry powder for inhalation) DryNeb Device

  Drug: NHT102 · Device: DryNeb

• Experimental
  Dose Optimization

  Participants are randomized 1:1 to one of two dose levels selected from Part 1. Each dose level is evaluated using Simon Two Stage design to assess anti-tumor activity, safety, pharmacokinetics, pharmacodynamics, and exploratory biomarkers. Up to approximately 25 evaluable patients may be enrolled per dose level.

  Drug: NHT102 · Device: DryNeb

• Experimental
  Dose Expansion

  Participants receive NHT102 at the recommended Phase 2 dose (RP2D) determined from Part 2. This part further evaluates safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity.

  Drug: NHT102 · Device: DryNeb

Interventions

• DrugNHT102

  NHT102 is an investigational drug product, 5-Azacytidine dry powder for oral inhalation. NHT102 is administered once daily via inhalation using a novel investigational inhalation delivery system. Dosing occurs on Days 1-5 and Days 15-19 of each 28-day cycle. Multiple dose levels (7 mg to 42 mg target lung dose per treatment day) are evaluated in Part 1, selected dose levels in Part 2, and the recommended Phase 2 dose (RP2D) in Part 3.

  Also known as: 5-AZA, 5-Azacytidine dry powder, NHT102-5-AZA, Azacitidine

• DeviceDryNeb

  The DryNeb is a novel investigational inhalation delivery system that delivers micronized dry powder to the lungs.

  Also known as: Clinical Benchtop DryNeb, Novel Inhalation Delivery System

Primary outcomes

1. Incidence and Severity of Adverse Events (AEs)

   Treatment emergent adverse events, serious adverse events, and clinically significant laboratory or vital sign abnormalities assessed using CTCAE v6.0 (Part I).

   Time frame: From first dose through 30 days after the last dose.

2. Incidence of dose-limiting toxicities (DLT)-Part I

   Number of participants experiencing DLTs during the DLT evaluation period, defined per protocol.

   Time frame: 28-day DLT evaluation period (Cycle 1)

3. Overall Response Rate (ORR)-Parts 2 and 3.

   Proportion of participants achieving complete or partial response per RECIST v1.1.

   Time frame: From first dose until first documented disease progression, date of death or patient withdrawal from the study for any reason, assessed up to six months.

4. Progression Free Survival (PFS)-Parts 2 and 3.

   Time from first dose to disease progression or death.

   Time frame: From first dose until first documented disease progression, date of death or patient withdrawal from the study for any reason, assessed up to six months.

5. Overall Survival (OS)-Parts 2 and 3.

   Time from first dose to death.

   Time frame: From first dose until first documented disease progression, date of death or patient withdrawal from the study for any reason, assessed up to six months.

6. Duration of Response (DOR)-Parts 2 and 3.

   Time from first observation of response to progression or death.

   Time frame: From first documented response to date of first documented disease progression, date of death or patient withdrawal from the study for any reason, assessed up to six months.

Secondary outcomes

1. Pharmacokinetic Parameters of NHT102-Parts 1, 2, and 3.

   To determine the PK parameter for the peak plasma concentration (Cmax).

   Time frame: At the end of Cycle 1. (Each cycle is 28 days)

2. Incidence and Severity of Adverse Events (AEs)-Parts 2 and 3.

   TEAEs, SAEs, and clinically significant abnormalities assessed using CTCAE v6.0.

   Time frame: From first dose through 30 days after the last dose.

3. Percent Change in DNA Methylation-Parts 2 and 3.

   Percent change in global DNA methylation in tumor and/or bronchial epithelium compared with pre treatment.

   Time frame: Baseline to post-treatment (estimated to be minimum of 7 months)

4. PK parameters of NHT102. Parts 1, 2, and 3.

   Area under the curve (AUC) plasma concentration versus time curve.

   Time frame: At the end of Cycle 1. (Each cycle is 28 days)

5. PK Parameters of NHT102. Parts 1, 2, and 3.

   Time to maximum plasma concentration (Tmax)

   Time frame: At the end of cycle 1. (Each cycle is 28 days)

6. PK parameters of NHT102. Parts 1, 2 and 3.

   Estimated time to reduce the plasma concentration by exactly one half (T1/2)

   Time frame: At the end of Cycle 1. (Each Cycle is 28 days)

Other outcomes

1. Percent Change in DNA Methylation - Part I.

   Percent change in global DNA methylation in tumor and/or bronchial epithelium compared with pre-treatment.

   Time frame: Baseline (Day 1) to post-treatment. (Estimated minimum of 7 months)

Individual participant data

Plan to share: No — At the current time, there are no plans to show de-identified individual patient data but only aggregate data.