Zipalertinib for Non-Small Cell Lung Cancer

(REZILIENT1 Trial)

Not currently recruiting at 84 trial locations

Overseen By Danny Nguyen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1 & 2

Sponsor: Cullinan Therapeutics Inc.

Must not be taking: CYP3A inhibitors, P-gp inducers

Disqualifiers: COVID-19 pneumonitis, Brain metastases, Cardiac conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CLN-081 for individuals with non-small cell lung cancer (NSCLC) that has a specific mutation in the EGFR gene. The trial aims to assess the safety and effectiveness of this treatment and determine the optimal dose for future studies. It consists of several parts, each examining different aspects of the treatment. Suitable candidates for this trial have advanced NSCLC with the EGFR mutation and have previously tried other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including those that affect gastrointestinal motility or gastric pH, and any drugs that are inhibitors or inducers of specific enzymes, at least 14 to 28 days before starting the study drug. It's best to discuss your current medications with the trial team to see if any need to be paused.

Is there any evidence suggesting that CLN-081 is likely to be safe for humans?

Research has shown that CLN-081 is a new treatment for people with non-small cell lung cancer (NSCLC) who have certain genetic changes. Studies have found that CLN-081 targets these changes, aiming to attack cancer cells while sparing healthy cells.

In earlier trials, most patients tolerated CLN-081 well, experiencing no severe side effects. Some common side effects were mild, such as skin rash or nausea. However, reactions can vary, and some individuals might experience other side effects.

Since the trial is in its early stages, the main goal is to determine the best dose and gather more information about the safety of CLN-081. The treatment has not yet received FDA approval, so ongoing trials are crucial for collecting additional safety data. Those considering joining a trial should discuss the potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about CLN-081 for non-small cell lung cancer (NSCLC) because it targets a specific mutation known as EGFR exon 20 insertion mutations, which are notoriously hard to treat with existing therapies. Most current treatments for NSCLC, like EGFR tyrosine kinase inhibitors (TKIs), struggle to effectively address these mutations. CLN-081 is distinctive because it is designed to work even in patients who have already tried other EGFR TKIs or systemic therapies without success. Additionally, the treatment is being tested in various dosing strategies to optimize its effectiveness and safety, potentially offering a more tailored approach for patients with this challenging mutation.

What evidence suggests that CLN-081 could be an effective treatment for non-small cell lung cancer?

Research has shown that CLN-081 may help treat non-small cell lung cancer (NSCLC) with a specific genetic change known as EGFR exon 20 insertion mutations. Early studies found that patients taking CLN-081 had good results, even after trying other treatments. This trial includes various treatment arms, such as dose escalation and expansion cohorts, to evaluate CLN-081's effectiveness. This genetic change usually leads to a worse outlook, but CLN-081 targets it effectively, which might improve survival rates. Data from trials have shown that the drug can control the disease and offer benefits where other treatments might not work as well. These findings suggest that CLN-081 could be a valuable option for patients with this difficult-to-treat cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Zosia Piotrowska, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called EGFR exon 20 insertion. Participants can be new to treatment or have had certain prior therapies, but not treatments targeting this specific mutation or CLN-081. They should be able to do light work and must not currently smoke or have used tobacco recently.

Inclusion Criteria

My cancer has a specific EGFR mutation confirmed by a certified test.

I have been treated with a drug approved for EGFR ex20ins mutant NSCLC.

I have advanced or metastatic non-small cell lung cancer.

Exclusion Criteria

I was hospitalized for lung problems due to COVID-19.

I haven't taken EGFR inhibitors for at least 8 days before starting the study drug.

I have a history of lung conditions not related to infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Determine the safety, tolerability, and preliminary anti-tumor activity of CLN-081 monotherapy in dose escalation cohorts

24 months

Phase 2a Dose Expansion

Evaluate the safety and efficacy of CLN-081 monotherapy in expansion cohorts

24 months

Module A

Preliminarily assess the effect of food on the PK profile of CLN-081

24 months

Module B

Further characterize the safety and efficacy of CLN-081 monotherapy in patients with prior systemic anti-cancer treatment

24 months

Module C

Explore the safety, tolerability, and efficacy of CLN-081 monotherapy in patients with prior treatment with an agent approved for EGFR exon 20 insertion mutant NSCLC

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CLN-081

Trial Overview The study is testing the safety and effectiveness of a drug named CLN-081 in patients with NSCLC who have the EGFR exon 20 insertion mutation. It's an early-stage trial aiming to find the best dose for Phase 2 and see how well it works against this type of lung cancer.

How Is the Trial Designed?

Group I: Phase 2a Dose Expansion(s) Experimental Treatment 1 Intervention

CLN-081 BID in expansion cohorts that may be opened at doses that meet pre-specified efficacy and safety criteria.

Group II: Phase 1 Dose Escalation (Rolling Six) Experimental Treatment 1 Intervention

CLN-081 BID in Rolling Six dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations.

Group III: Phase 1 Dose Escalation (Accelerated Titration) Experimental Treatment 1 Intervention

CLN-081 BID in single patient dose escalation cohorts enrolling NSCLC patients with EGFR exon 20 insertion mutations that either have received or never received prior EGFR TKIs.

Group IV: Module C Experimental Treatment 1 Intervention

CLN-081 BID to patients with EGFR exon 20 insertion mutant NSCLC after prior therapy with an agent approved for the treatment of ex20ins mutant NSCLC.

Group V: Module B Experimental Treatment 1 Intervention

CLN-081 BID in NSCLC patients with EGFR exon 20 insertion mutations that have received prior systemic therapy for locally advanced or metastatic disease.

Group VI: Module A Food Affect Experimental Treatment 1 Intervention

Single-dose CLN-081 150 mg with and without high fat food intake.

Who Is Running the Clinical Trial?

Cullinan Therapeutics Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Cullinan Pearl

Lead Sponsor

Trials

1

Recruited

280+

Cullinan Oncology, LLC

Lead Sponsor

Trials

7

Recruited

990+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9007

Phase (Ph) 1/2a study of CLN-081 in patients (pts) with ... We present updated results of the initial multicenter Ph1/2a study of CLN-081 in pts with advanced, EGFR ins20-mutant NSCLC, including 39 pts ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04036682

NCT04036682 | A Phase 1/2 Trial of CLN-081 in Patients ... The objective of Module B is to further characterize the safety and efficacy of CLN-081 monotherapy in patients with EGFR exon 20 insertion mutation NSCLC who ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11106363/

Current status and breakthroughs in treating advanced non ... Currently, there is a lack of effective treatments for EGFR ex20ins mutations NSCLC. The efficacy of chemotherapy has been relatively favorable.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0305737223000981

EGFR exon20 insertion mutations in non-small cell lung ... Patients with NSCLC harboring EGFR ex20ins are known to have poorer prognosis than those with other EGFR-TKI sensitive mutations.

5. ir.zailaboratory.com ir.zailaboratory.com/news-releases/news-release-details/cullinan-oncology-present-updated-data-highlighting-therapeutic

Cullinan Oncology to Present Updated Data Highlighting ... Cullinan is evaluating various doses of CLN-081 in a Phase 1/2a trial in patients with NSCLC harboring EGFR exon 20 mutations who have received prior therapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9008900/

EGFR exon 20 insertion mutations in advanced non-small- ... CLN-081 is a new oral EGFR-TKI that has a wide range of activities against clinically relevant EGFR mutations (including ex20ins mutations). In ...