INV-1120 + Pembrolizumab for Advanced Cancer

(KEYNOTE-E12 Trial)

Recruiting at 2 trial locations

Overseen By radhika Shah, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Shenzhen Ionova Life Sciences Co., Ltd.

Must not be taking: H2 blockers, Proton pump inhibitors

Disqualifiers: Cancer, Autoimmune, Infections, Cardiac, others

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

Compensation: Varies

Number of Visits: Unknown

78 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1, open-label dose-escalation study to determine the MTD of INV-1120 and RP2D, and to assess the DLT of INV-1120 as a single agent or in the combination with pembrolizumab. The safety, tolerability, and PK of INV-1120 as a single agent or in the combination with pembrolizumab will be assessed in adult patients with advanced solid tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain medications, like those causing Torsades de Pointes, H2 blockers, and proton pump inhibitors, require a washout period (time without taking them) before starting the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Pembrolizumab has shown effectiveness in improving survival and response rates in various cancers, such as non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It has been approved for use in these conditions based on clinical trials demonstrating significant benefits in survival and disease progression. ^{1 2 3 4 5}

What safety information is available for Pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been studied in various cancers and is generally well tolerated, but it can cause side effects like fatigue, rash, itching, and diarrhea. Some less common but serious side effects include immune-related issues like inflammation of the lungs (pneumonitis), liver (hepatitis), and thyroid problems. ^{1 2 5 6 7}

What makes the drug INV-1120 + Pembrolizumab unique for advanced cancer?

This treatment combines INV-1120 with pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. Pembrolizumab is already used for various cancers, but combining it with INV-1120 may offer a new approach for advanced cancer by potentially enhancing the immune response. ^{1 2 8 9 10}

Eligibility Criteria

Adults with advanced solid tumors who've tried standard treatments or have none available. They must be over 18, able to swallow pills, not pregnant, and agree to use two forms of contraception. Excluded are those with certain infections, brain metastases, recent major surgery or heart issues, and severe allergies.

Inclusion Criteria

Written informed consent, according to local guidelines, signed and dated by the patient prior to the performance of any study-specific procedures, sampling, or analyses

Patient must be ≥18 years-of-age at the time of signature of the informed consent form (ICF)

Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

Exclusion Criteria

Known malignant central nervous system disease other than neurologically stable, treated brain metastases - defined as metastases having been treated by surgery, surgery plus radiotherapy or radiotherapy alone, with no evidence of progression or hemorrhage and off any systemic corticosteroids for at least 4 weeks prior to signing the consent

History (within 4 weeks of starting treatment) or evidence of active infections (Grade ≥2)

Seropositive status for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at any time before the start of treatment: Testing for seropositive status during screening will be at the discretion of the Investigator in patients without previously reported results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Treatment

Participants receive escalating doses of INV-1120 orally once a day until unacceptable toxicity or disease progression. Safety and pharmacokinetics are evaluated.

28 days per cohort

Multiple visits for dose escalation and safety evaluation

Phase 1b Treatment

Participants receive escalating and de-escalating doses of INV-1120 in combination with pembrolizumab until unacceptable toxicity or disease progression. Safety and pharmacokinetics are evaluated.

21 days per cohort

Multiple visits for dose escalation and safety evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• INV-1120
• Pembrolizumab

Trial Overview The trial is testing INV-1120 alone and combined with Pembrolizumab in adults with advanced solid tumors. It's an early-phase study to find the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety, tolerability, and how the body processes these drugs.

Participant Groups

Group I: Dose Escalation Experimental Treatment 2 Interventions

Phase 1a: Subjects will receive escalating doses of INV-1120 orally once a day until un-acceptable toxicity or disease progression. Three to six patients will be enrolled per cohort to evaluate the safety and pharmacokinetics for each dose level. After the last patient in each cohort completes Cycle 1 (DLT observation period of 28 days), the Safety Evaluation Team (SET) will evaluate the safety data and pharmacokinetic collected from Cycle 1, and make the decision whether to escalate the dose before opening the second cohort. Phase 1b: Subjects will receive escalating and de-escalating doses of INV-1120 orally once a day in combination with pembrolizumab until un-acceptable toxicity or disease progression, and DLT observation period of 21 days.

Who Is Running the Clinical Trial?

Shenzhen Ionova Life Sciences Co., Ltd.

Lead Sponsor

Trials

2

Recruited

140+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In the KEYNOTE-189 study involving 616 patients with metastatic non-squamous non-small-cell lung cancer, the combination of pembrolizumab and pemetrexed-platinum significantly maintained quality of life (GHS/QOL) scores compared to placebo, with a notable improvement at week 21.

Patients receiving pembrolizumab also experienced a longer median time to deterioration in symptoms like cough and chest pain, although this result was not statistically significant, indicating potential benefits in symptom management with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Garassino, MC., Gadgeel, S., Esteban, E., et al.[2020]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab demonstrated antitumor activity in patients with classic and endemic Kaposi sarcoma, indicating its potential as a treatment option for this type of cancer.

The findings suggest that pembrolizumab, an immune checkpoint inhibitor, may effectively enhance the immune response against Kaposi sarcoma tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Is Safe and Effective in Kaposi Sarcoma. [2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. [2020]

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

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

Pembrolizumab Is Safe and Effective in Kaposi Sarcoma. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. [2023]