Chemotherapy + Retifanlimab for Cancer

No longer recruiting at 128 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of adding Retifanlimab, a type of immunotherapy, to the existing chemotherapy regimen of Carboplatin and Paclitaxel for treating squamous cell anal carcinoma (SCAC) that is locally recurrent or metastatic and cannot be surgically removed. Researchers aim to determine if this combination improves outcomes compared to the standard treatment. The trial includes two groups: one receiving the combination with Retifanlimab and the other with a placebo. It seeks participants with SCAC who have not undergone prior systemic chemotherapy and can provide recent biopsy samples. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

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

Previous studies have found that combining retifanlimab with carboplatin and paclitaxel is relatively safe, though some risks exist. Neutropenia, a condition characterized by low levels of white blood cells that fight infections, was the most common serious side effect. It occurred in about 35% of patients taking the retifanlimab combination, compared to about 30% of those who received a placebo instead of retifanlimab.

Adrenal insufficiency, where the adrenal glands don't produce enough hormones, affected about 6% of patients. Overall, the treatment has a manageable safety profile, indicating that while side effects can occur, they can often be monitored and treated effectively. This suggests the treatment is generally well-tolerated, though some risks remain. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about retifanlimab because it offers a new approach to cancer treatment. Unlike the standard chemotherapy options like carboplatin and paclitaxel, which attack cancer cells broadly, retifanlimab is an immune checkpoint inhibitor. It works by targeting the PD-1 pathway to help the immune system recognize and attack cancer cells more effectively. This mechanism has the potential to enhance the body's natural defenses against tumors, offering hope for improved outcomes in cancer therapy.

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

This trial will compare two treatment groups for squamous cell anal carcinoma (SCAC). Group A will receive carboplatin and paclitaxel with a placebo, while Group B will receive carboplatin, paclitaxel, and retifanlimab. Research has shown that combining retifanlimab with carboplatin and paclitaxel is promising for treating SCAC. Specifically, studies demonstrated that this combination helped patients live longer without disease progression. Adding retifanlimab reduced the risk of cancer worsening or causing death by 37%. Additionally, this treatment combination led to a higher rate of cancer shrinking or disappearing. These findings suggest that adding retifanlimab to standard chemotherapy could be more effective for advanced SCAC than chemotherapy alone. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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]

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]

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-retifanlimab-dlwr-carboplatin-and-paclitaxel-and-single-agent-squamous-cell-carcinoma

FDA approves retifanlimab-dlwr with carboplatin and ... The major efficacy outcome measures were ORR and DOR as assessed by an independent review committee (IRC) according to RECIST v1.1. ORR was 14% ...

2. onclive.com onclive.com/view/retifanlimab-plus-carboplatin-and-paclitaxel-offers-pfs-benefit-in-recurrent-metastatic-scac

Retifanlimab Plus Carboplatin and Paclitaxel Offers PFS ... Retifanlimab combined with carboplatin and paclitaxel significantly improved progression-free survival in advanced SCAC patients compared to ...

3. investor.incyte.com investor.incyte.com/news-releases/news-release-details/phase-3-data-incytes-retifanlimab-zynyzr-patients-squamous-cell

Phase 3 Data for Incyte's Retifanlimab (Zynyz®) in Patients ... Adding retifanlimab to carboplatin and paclitaxel resulted in a clinically meaningful 37% reduction in the risk of progression or death (Hazard ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40517007/

Retifanlimab with carboplatin and paclitaxel for locally ... The most common grade ≥3 adverse events were neutropenia (35·1% for retifanlimab plus carboplatin-paclitaxel vs 29·6% for placebo plus ...

5. zynyzhcp.com zynyzhcp.com/scac/efficacy

Efficacy for SCAC | ZYNYZ® (retifanlimab-dlwr) for HCPs ZYNYZ in Combination with Carboplatin and Paclitaxel: Adrenal insufficiency occurred in 5.8% (9/154) of patients receiving ZYNYZ in combination with carboplatin ...