Tomivosertib for Non Small Cell Lung Cancer

(KICKSTART Trial)

Recruiting at 105 trial locations

Overseen By Mark Densel

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Effector Therapeutics

Must be taking: Pembrolizumab

Must not be taking: Prednisone

Disqualifiers: EGFR, ALK, GI disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two drugs, Tomivosertib and pembrolizumab, in patients with a specific type of lung cancer. Pembrolizumab is a targeted therapy that has been approved for treating this type of cancer. The trial aims to enhance the immune system's ability to fight cancer, especially in those who haven't been treated yet or whose cancer has worsened despite previous treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants must not have been treated with certain chemotherapy recently, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Tomivosertib + Pembrolizumab for Non-Small Cell Lung Cancer?

Research shows that pembrolizumab, a part of this drug combination, has been effective in treating non-small cell lung cancer by improving progression-free survival compared to traditional chemotherapy. Additionally, pembrolizumab has shown promising results in patients with advanced stages of this cancer. ^{1 2 3 4 5}

What safety data exists for pembrolizumab in treating non-small cell lung cancer?

Pembrolizumab, used for non-small cell lung cancer, has been associated with treatment-related side effects like rash, fatigue, and hypothyroidism (underactive thyroid). Some patients experience immune-related side effects, which can be severe, especially in those with good health status and high PD-L1 expression. These side effects are important to monitor during treatment. ^{3 6 7 8 9}

What makes the drug Tomivosertib + Pembrolizumab unique for treating non-small cell lung cancer?

Tomivosertib combined with Pembrolizumab is unique because it pairs a novel investigational drug, Tomivosertib, with Pembrolizumab, an established immunotherapy that blocks PD-1 (a protein that helps cancer cells hide from the immune system). This combination aims to enhance the immune response against cancer cells, potentially offering a new approach for patients with non-small cell lung cancer. ^{1 3 4 10 11}

Research Team

Douglas Warner, MD

Principal Investigator

EFFECTOR Therapeutics, Inc.

Eligibility Criteria

Inclusion Criteria

Are you taking medication for you depression?

Answer YES if you have not been treated with platinum-based chemotherapy (e.g., cisplatin, carboplatin, and oxaliplatin)

Do you have a tumor PD-L1 that is at least 50%? PD-L1 protein prevents immune cells from attacking harmless cells. Check your biomarker test results for PD-L1 level.

Exclusion Criteria

You have advanced or metastatic non-small cell lung cancer and your tumor tests positive for PD-L1 with a score of 50 or more. You also meet the requirements for treatment with pembrolizumab.

Can you move around easily and do light work during the day? Answer YES or NO.

The doctors need to review the two most recent scans, which show that your condition is getting worse.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tomivosertib in combination with pembrolizumab, with or without pemetrexed, depending on NSCLC type

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• Pemetrexed
• Tomivosertib

Participant Groups

Group I: C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous) Experimental Treatment 3 Interventions

Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive tomi plus pembrolizumab and pemetrexed (non-squamous NSCLC) or tomi plus pembro as a single agent (squamous) in accordance with the package insert.

Group II: B1 Tomi + Pembro Experimental Treatment 2 Interventions

Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib.

Group III: A1 Tomi + Current Pembro Experimental Treatment 2 Interventions

Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab.

Group IV: Pbo + Pembro Placebo Group 1 Intervention

Subjects will initiate pembrolizumab as first-line therapy and receive matching placebo.

Group V: Pbo + Current Pembro Placebo Group 1 Intervention

Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert, will receive matching placebo in addition to pembrolizumab.

Group VI: Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous) Placebo Group 2 Interventions

Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive placebo plus pembrolizumab and pemetrexed (non-squamous NSCLC) or placebo plus pembro as a single agent (squamous) in accordance with the package insert.

Who Is Running the Clinical Trial?

Effector Therapeutics

Lead Sponsor

Trials

11

Recruited

600+

ICON plc

Industry Sponsor

Trials

88

Recruited

28,900+

Dr. Steve Cutler

ICON plc

Chief Executive Officer since 2017

PhD from the University of Sydney, MBA from the University of Birmingham

Dr. Greg Licholai

ICON plc

Chief Medical Officer since 2023

Degrees from Harvard Business School, Yale School of Medicine, Columbia University, and Boston College

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Findings from Research

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study of 43 patients with non-small cell lung cancer, nivolumab showed the highest median progression-free survival (12.6 months) and overall survival (13.4 months), particularly in patients with fewer metastases and better performance status.

While 85% of patients experienced some adverse effects, the development of vitiligo in patients treated with nivolumab was associated with a more durable response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. Burgos-San José, A., Colomer-Aguilar, C., Martínez-Caballero, D., et al.[2021]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In a study of 97 non-small cell lung cancer patients treated with pembrolizumab, 40% experienced treatment-related adverse events (trAEs), with common ones being rash, fatigue, and hypothyroidism.

Patients who experienced trAEs had significantly better clinical outcomes, including a higher objective response rate (38.5% vs. 8.9%), longer progression-free survival (248 days vs. 60 days), and longer overall survival (493 days vs. 144.5 days), suggesting that trAEs may be indicative of a positive response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. Lisberg, A., Tucker, DA., Goldman, JW., et al.[2022]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

In a study of patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab, a higher overall tumor burden was associated with a lower incidence of severe immune-related adverse events (irAEs), suggesting that tumor size may influence treatment safety.

Good performance status and high PD-L1 expression were significant predictors of developing severe irAEs, with odds ratios of 3.27 and 4.44, respectively, indicating that patients with these characteristics should be closely monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. Sumi, T., Koshshino, Y., Sekikawa, M., et al.[2022]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

2. Spain pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Association of Immune-Related Adverse Events and Efficacy Outcomes With Consolidation Pembrolizumab After Chemoradiation in Patients With Inoperable Stage III Non-Small-Cell Lung Cancer. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]