Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination With Paclitaxel in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy

NCT05283226 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NAT2694US
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 13

Brief Summary

This is a Phase 2, open-label, multicenter, single-arm study of NRC-2694-A in combination with paclitaxel in patients with R/M HNSCC with progression on or after ICI therapy. A total of approximately 46 male and female patients will be enrolled. This sample size is based on Simon's 2-stage design with historical control ORR of 30% and a target ORR of 50%.

Conditions

Carcinoma; Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Keywords

Carcinoma; Recurrent and/or Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• To determine if NRC-2694-A administered orally in combination with paclitaxel demonstrates objective response in patients with R/M HNSCC, who have had radiological progression on or after treatment with ICI therapies like pembrolizumab or nivolumab

  Objective response in terms of CR/PR per RECIST v1.1

  Baseline through approximately up to 24 weeks

Secondary Outcomes (19)

• Progression-free survival

  Baseline through approximately up to 24 weeks

• Overall survival

  Baseline through approximately up to 24 weeks

• Duration of response

  Baseline through approximately up to 24 weeks

• Clinical benefit response

  Baseline through approximately up to 26 weeks

• Number of adverse events

  Baseline through approximately up to 24 weeks

Other Outcomes (3)

• To determine the association between NRC-2694-A activity and biomarkers in blood samples using Epidermal growth factor receptor status in EGFR (epidermal growth factor receptor) gene

  Baseline through approximately up to 24 weeks

• To determine the association between NRC-2694-A activity and biomarkers in blood samples using downstream signaling in EGFR gene

  Baseline through approximately up to 24 weeks

• To determine the association between NRC-2694-A activity and biomarkers in blood samples using mutations in EGFR gene

  Baseline through approximately up to 24 weeks

Study Arms (1)

NRC-2694-A In Combination with paclitaxel

EXPERIMENTAL

Patients will receive NRC-2694-A 300 mg orally once daily and paclitaxel 175 mg/m² IV infusion over approximately 3 hours once in 21 days for 6 cycles or more.

Drug: NRC-2694-A; Drug: Paclitaxel

Interventions

NRC-2694-A DRUG

300 mg orally once daily

NRC-2694-A In Combination with paclitaxel

Paclitaxel DRUG

175 mg/m² IV infusion over approximately 3 hours

NRC-2694-A In Combination with paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is willing and capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Is male or female aged 18 years or older at the time of consent.
• Has histologically confirmed unresectable R/M HNSCC (oral cavity, oropharynx, hypopharynx, and larynx).
• Has documented progressive disease assessed by the principal investigator according to RECIST v1.1.
• Has a measurable lesion per RECIST v1.1.
• Has ECOG performance status score of ≤2.
• Must have progressed during or after receiving ICI therapy, such as pembrolizumab or nivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg, pembrolizumab or nivolumab) and who had recovered prior to study entry will also be eligible.
• Female patients of childbearing potential should have a negative urine test before enrollment. If the urine pregnancy test is positive or gives equivocal results, a serum pregnancy will be required for confirmation.
• Patients of reproductive age must use acceptable methods of contraception throughout the study period and for 30 days following the last dose of investigational product (see protocol for further guidance).
• During screening and at subsequent visits, the investigator should ensure adequate bone marrow reserve (neutrophil count ≥1500/mm3, platelet count ≥100,000/mm3, and hemoglobin level 8.0 g/dL), renal function (creatinine clearance ≥30 mL/min calculated by Cockcroft-Gault formula), liver function (total bilirubin level ≤1.5 × ULN \[except patients with documented Gilbert's syndrome\] and serum transaminase levels ≤2.5 × ULN or ≤5 × ULN for liver metastasis and/or obstructive jaundice).
• Must have completed a duration of at least two weeks after stopping ICI therapy/investigational therapy/salvage therapy and must have recovered to grade ≤1 from all toxicities due to such therapies.

You may not qualify if:

• Has cardiac, hepatic, endocrine, pulmonary, or autoimmune disease, interstitial lung disease, renal or psychiatric disorders, not controlled with therapy corresponding to the illness or a condition that contraindicates the use of a taxane or an EGFR inhibitor.
• Has Cirrhosis of liver at a level of Child-Pugh B (or worse).
• Has uncontrolled brain metastases. Patients are allowed if brain metastasis has been previously treated with surgery, whole brain irradiation, and/or stereotactic radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of prednisone or equivalent) at the time of the first dose of investigational product. Radiological evaluation of brain metastasis will be performed only if the patient has symptoms. For asymptomatic patients, brain imaging during screening is not required.
• Has baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>480 milliseconds \[CTCAE Grade 1\] using Fredericia's QT correction formula).
• Has a history of additional risk factors for Torsade de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
• Has had prior cetuximab therapy for recurrent or metastatic disease. Note that cetuximab used concomitantly with radiotherapy or as an induction therapy is acceptable
• Has received any other EGFR-targeted therapies for recurrent or metastatic disease.
• Currently participating in any clinical trial or receiving investigational therapy on expanded access or compassionate basis.
• Has nasopharyngeal carcinomas or salivary gland cancers.
• Female patient who tested positive for pregnancy.
• Female patient who is breastfeeding or planning to become pregnant, or male patient planning to father a child within the duration of the study.
• Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However, patients who test positive for HCV antibody, but negative for HCV RNA, will be allowed. In addition, patients with controlled HIV, chronic HBV on suppressive antiviral therapy, or a history of HCV infection status post-curative antiviral treatment with an HCV viral load below limit of quantification are permitted to participate (DHHS 2020).
• Has active infection requiring intravenous anti-infective therapy within 7 days prior to Day 1 Cycle 1 or is febrile due to infection.
• Has had major surgery within 4 weeks prior to screening.
• Administered a live attenuated vaccine within 4 weeks prior to Day 1 Cycle 1 or anticipation that such a live attenuated vaccine will be required during the study.

Sponsors & Collaborators

• NATCO Pharma Ltd.: lead

Study Sites (13)

Providence Medical Foundation -Fullerton

Fullerton, California, 92835, United States

COMPLETED

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, 90017, United States

COMPLETED

Lynn Cancer Center

Boca Raton, Florida, 33486, United States

COMPLETED

Miami Cancer Center

Miami, Florida, 33176, United States

COMPLETED

Norton Cancer Institute - Downtown

Louisville, Kentucky, 40202, United States

COMPLETED

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201-1544, United States

COMPLETED

Washington University - Siteman Cancer Center

St Louis, Missouri, 63110, United States

COMPLETED

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756-1000, United States

COMPLETED

Salib Oncology

Easton, Pennsylvania, 18045, United States

COMPLETED

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

COMPLETED

Daycare Angels under AOH

Mumbai, Maharashtra, 40001, India

RECRUITING

Grant Medical Foundation Ruby Hall Clinic

Pune, Maharashtra, 411001, India

COMPLETED

Basavatarakam Indo American Cancer Hospital & Research Institute

Hyderabad, Telangana, 500034, India

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Praveen Myneni, MBBS

CONTACT

+91 40 23547532; drpraveen@natcopharma.co.in

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: March 16, 2022
• Study Start: September 30, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (3); US (10)