INV-1120 + Pembrolizumab for Advanced Cancer

(KEYNOTE-E12 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new drug, INV-1120, both alone and with pembrolizumab (KEYTRUDA, an immunotherapy drug), to treat advanced solid tumors unresponsive to standard treatments. The goal is to determine the safest dose and understand how patients' bodies respond to these medicines. The study is open to individuals with advanced solid tumors whose disease has progressed after standard therapies and who have at least one tumor measurable by scans like CT or MRI. Participants must be able to swallow pills and have a life expectancy of at least three months. 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 this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that INV-1120 is generally well-tolerated by patients with advanced solid tumors. In studies, patients maintained stable disease without serious side effects, indicating that INV-1120 is relatively safe when used alone.

Pembrolizumab, already approved for treating various cancers, has been tested in many patients and is generally considered safe, though some may experience side effects like tiredness or a rash.

The safety of combining INV-1120 with pembrolizumab remains under investigation. However, understanding the safety of each drug individually provides some confidence. This trial aims to determine how well patients tolerate the combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about INV-1120 in combination with pembrolizumab for advanced cancer because it offers a fresh approach to treatment. While pembrolizumab is a well-known immunotherapy that helps the immune system attack cancer, INV-1120 adds a unique angle by potentially enhancing the immune response. It works differently than typical treatments by targeting specific pathways that might improve the effectiveness of pembrolizumab. This combination could lead to better outcomes for patients with advanced cancer, offering hope for more effective and personalized treatment options.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that INV-1120 could be a promising treatment for advanced solid tumors. In this trial, participants will receive escalating doses of INV-1120, with some also receiving it in combination with pembrolizumab—a drug proven effective for various cancers. Early studies found that most patients tolerated INV-1120 well, with some experiencing stable disease for an extended period. Past studies have demonstrated significant survival benefits with pembrolizumab, with long-term evidence supporting its use. Together, these treatments may offer hope for people with advanced cancer. However, further research is needed to confirm their combined effectiveness. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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

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

Patients with life expectancy ≥3 months

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 (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 (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 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]

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]

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, 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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04443088

An Open-Label Study of INV-1120 As a Single Agent and ... 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 ...

2. access.portico.org access.portico.org/Portico/show?viewFile=pdf&auId=pjbcqwwkr7x

Society for Immunotherapy of Cancer (SITC) – 37th Annual ... The results presented in this preliminary study were based only on the dose-escalation part of INV-1120 monother- apy (phase Ia), and the assessment of phase Ib ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4141207/

A phase I, open-label dose-escalation study of continuous ... This phase I, open-label dose-escalation study investigated BIBF 1120 combined with paclitaxel (Taxol) and carboplatin in first-line patients with advanced ( ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e14579

Preliminary safety, efficacy, and pharmacokinetics (PK) ... Conclusions: Single agent INV-1120 was generally well tolerated in the Chinese population and showed preliminary signs of antitumor activity in ...

5. onclive.com onclive.com/view/inv-1120-proves-tolerable-in-advanced-solid-tumors-moves-to-expansion-in-combination-with-pembrolizumab

INV-1120 Proves Tolerable in Advanced Solid Tumors ... “Single-agent INV-1120 was well tolerated in patients with advanced solid tumors. Five of 24 patients showed stable disease for at least 18 ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT414438

Preliminary safety, efficacy, and pharmacokinetics (PK) ... Single agent INV-1120 was generally well tolerated in the Chinese population and showed preliminary signs of antitumor activity in terms of stable disease.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04443088/

Clinical Trial: NCT04443088 The safety, tolerability, and PK of INV-1120 will be assessed in adult patients with advanced solid tumors. Increasing doses of INV-1120 will be ...