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

Condition(s) studied

Investigational drug(s) / intervention(s)

NHT102: 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.

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

Study summary

There are 3 parts to this clinical trial. The goal of this clinical trial (NHT102-001) is to learn how safe NHT102 is, what dose works best, and whether it can help treat advanced non-small cell lung cancer (NSCLC) that has come back or remained after earlier treatment and is still confined to the lung / chest region by providing targeted inhaled treatment directly to the lungs. NHT102 is a dry powder that participants breathe in through a mouthpiece using an investigational inhalation device. Doses are given at the study site by trained staff, not at home. NHT102 is taken on days 1-5 and days 15-19 of a 28-day cycle.

The main questions this clinical trial aims to answer are:

Part 1 (Dose Escalation): To look at up to five different increasing dose levels of NHT102 to see if they are safe and well-tolerated and if the body absorbs the medicine from the lungs. To see if up to two dose levels studied are not only safe, but also make the cancer slow its growth or lessen its spread. And to see the highest dose that is tolerated by participants.

Part 2 (Dose Optimization): To further study at up to two dose levels from Part 1 and randomly assign participants in equal numbers to one of them to learn more about NHT102's safety, how well the drug is absorbed from the lungs and how well each dose level works against the NSCLC after at least 4 months. Then identify which of the two doses is chosen for further study.

Part 3 (Dose Expansion): Take the dose chosen in from Part 2 and study it in more patients to continue look at the drug safety, how much of it is absorbed into the body from the lungs and if it works to stop or reduce the spread of NSCLC.

Participants will:

* Take NHT102 at the study site daily on days 1-5 days and days 15-19 during a 28-day cycle for as long as it is helping them and they can tolerate it. Treatment stops if the cancer worsens, if side effects become too difficult to manage, or if the participant or their doctor decides to stop.
* Tell doctors and staff about all medications they are taking, any issues with their study medication and all side effects they may be having whether they are taking the medication that day or not.
* Return for a safety visit about 30 days after their last dose, then receive phone calls about 3 months and 6 months later to check on their health.

Eligibility

Primary outcome measure(s)

• Incidence and Severity of Adverse Events (AEs) — From first dose through 30 days after the last dose.
  Treatment emergent adverse events, serious adverse events, and clinically significant laboratory or vital sign abnormalities assessed using CTCAE v6.0 (Part I).
• Incidence of dose-limiting toxicities (DLT)-Part I — 28-day DLT evaluation period (Cycle 1)
  Number of participants experiencing DLTs during the DLT evaluation period, defined per protocol.
• Overall Response Rate (ORR)-Parts 2 and 3. — 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.
  Proportion of participants achieving complete or partial response per RECIST v1.1.
• Progression Free Survival (PFS)-Parts 2 and 3. — 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.
  Time from first dose to disease progression or death.
• Overall Survival (OS)-Parts 2 and 3. — 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.
  Time from first dose to death.
• Duration of Response (DOR)-Parts 2 and 3. — 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.
  Time from first observation of response to progression or death.

Trial sites (1)

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