Chemotherapy + Retifanlimab for Cancer

Recruiting at 106 trial locations

Overseen By Incyte Corporation Call Center (US)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must be taking: Antiretrovirals

Must not be taking: PD-(L)1 inhibitors

Disqualifiers: Second malignancy, Significant disorders, Infections, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 28

Duration: Up to 4.5 years

308 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a Phase 3 global, multicenter, placebo-controlled double-blind randomized study that will enroll participants with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.

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 mentions that current use of certain prohibited medications is not allowed. It's best to discuss your specific medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug combination of chemotherapy and Retifanlimab for cancer?

Research shows that combining chemotherapy drugs like carboplatin and paclitaxel with immunotherapy drugs has improved survival in patients with advanced non-small cell lung cancer. This suggests that similar combinations, like chemotherapy with Retifanlimab, might also be effective. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs like Carboplatin and Paclitaxel safe for use in humans?

The combination of Carboplatin and Paclitaxel has been studied in various cancers, showing moderate toxicity with some side effects like myelosuppression (a decrease in bone marrow activity) and neutropenia (low white blood cell count), but generally manageable and not life-threatening. These drugs have been used in different cancer treatments with known safety profiles, suggesting they are generally safe for human use in clinical settings. ^{2 6 7 8 9}

What makes the chemotherapy treatment with Carboplatin, Paclitaxel, and Retifanlimab unique?

This treatment combines Carboplatin and Paclitaxel, which are known for their effectiveness in various cancers, with Retifanlimab, a newer drug that may enhance the immune system's ability to fight cancer. The inclusion of Retifanlimab could potentially improve outcomes by leveraging its novel mechanism of action, which is different from traditional chemotherapy. ^{2 5 8 10 11}

Eligibility Criteria

This trial is for adults with inoperable locally recurrent or metastatic squamous cell anal carcinoma (SCAC) who haven't had systemic chemotherapy. Participants must be able to perform daily activities with little assistance, have measurable disease, provide tissue and blood samples, and if HIV-positive, meet certain health criteria. Pregnant or breastfeeding individuals can't join, nor those with recent radiotherapy or certain infections.

Inclusion Criteria

You must be willing to prevent pregnancy or having children during the study.

I am HIV-positive with stable health, meeting all required health criteria.

My cancer is confirmed and cannot be removed by surgery.

Exclusion Criteria

I have not had another type of cancer in the past 3 years.

I have had an organ or stem cell transplant.

Participant is pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carboplatin on Day 1, paclitaxel on Days 1, 8, and 15, and either retifanlimab or placebo on Day 1 of each 28-day cycle

Up to 4.5 years

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events

90 days after last dose

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Retifanlimab

Trial Overview The study tests the effectiveness of carboplatin-paclitaxel combined with either retifanlimab (a new drug) or a placebo in treating SCAC. It's a Phase 3 trial where participants are randomly assigned to one of the two groups without knowing which one they're in (double-blind).

Participant Groups

Group I: Group B : carboplatin+paclitaxel+retifanlimab Experimental Treatment 3 Interventions

Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle

Group II: Group A : carboplatin+paclitaxel+placebo Placebo Group 2 Interventions

Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

A phase I/II trial involving 46 patients with untreated advanced non-small cell lung cancer (NSCLC) demonstrated that the combination of carboplatin, nab-paclitaxel, and pembrolizumab is a safe and effective treatment, achieving a median overall survival of 15.4 months.

The study found a 35% overall response rate and a median progression-free survival of 5.6 months, indicating that this regimen can provide a durable benefit for patients, regardless of their PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Gentzler, RD., Mohindra, NA., Jalal, SI., et al.[2023]

In a phase III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

The combination of docetaxel and cisplatin showed a response rate of 32% and a median survival of 11.5 months in patients with advanced non-small-cell lung cancer (NSCLC), indicating its efficacy as a treatment option.

When combined with carboplatin, docetaxel demonstrated an improved response rate of 36% and a longer median survival of 13.9 months, suggesting that this combination may have a better safety profile and therapeutic index compared to the cisplatin combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in combination with platinum compounds for non small-cell lung cancer. Belani, CP.[2019]

In a phase II trial involving 55 patients with limited-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed promising efficacy, with 37.1% achieving a complete response and 51.4% a partial response.

The treatment was associated with moderate toxicity, primarily hematologic, but no life-threatening complications were reported, indicating that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. Gatzemeier, U., Jagos, U., Kaukel, E., et al.[2015]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. [2023]

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

Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: a phase II study. [2020]

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

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. [2023]

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

Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer: SWOG S0536. [2023]

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

Docetaxel in combination with platinum compounds for non small-cell lung cancer. [2019]

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

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. [2015]

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

Carboplatin alone or in combination in high-risk acute nonlymphoblastic leukemia. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

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

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

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

Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[Chemotherapy of small cell bronchial cancer with a combination of carboplatin, vincristine and etoposide]. [2015]