Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Nimotuzumab

Antineoplastic Agents, Immunological

Patients will receive weekly injections of Nimotuzumab (200mg/injection) for 12 weeks and standard external beam radiotherapy

200mg Nimotuzumab once a week for 12 weeks

IMRT radiation therapy with doses varying from 45Gy-54Gy in 25-30 fractions

Intensity Modulated Radiation Therapy (IMRT)

Te Vuong, MD

The objective of this study is to demonstrate the feasibility of using Nimotuzumab and radiation in the treatment of squamous cell carcinomas of the anal canal in order to achieve a 65% local control rate with a better toxicity profile than the conventional treatment. Patients with high toxicity risks (HIV+ and fragile patients) will be selected for this study.

Nimotuzumab With Radiotherapy in the Treatment of Anal Canal Cancers

A Phase II Clinical Study Using Nimotuzumab in Combination With External Beam Radiation Therapy in the Treatment of Patients With Carcinomas of the Anal Canal

Toxicity evaluation will include all toxicities occurring while the patient is receiving treatment, and will be monitored using the CTCAE guide version 3.0.

Tumor response rates will be evaluated using the MRI performed at 8-weeks post end of radiotherapy treatment.

YM BioSciences

Dr. Te Vuong

MD-Director Radiation Oncology

Neoplasms, Squamous Cell

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mitoguazone

Retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W).

Retifanlimab

Incyte Medical Monitor

The purpose of this study is to assess the efficacy of INCMGA00012 in participants with locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) who have progressed after platinum-based chemotherapy.

A Study of INCMGA00012 in Squamous Carcinoma of the Anal Canal Following Platinum-Based Chemotherapy (POD1UM-202)

A Phase 2 Study of INCMGA00012 in Participants With Squamous Carcinoma of the Anal Canal Who Have Progressed Following Platinum-Based Chemotherapy (POD1UM-202)

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as assessed by independent central radiographic (ICR) review, at any post-Baseline visit until new anti-cancer therapy or first Progressive Disease. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

DOR was defined as the time from an initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by ICR, or death due to any cause. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

DCR was defined as the percentage of participants with a confirmed overall response of CR, PR, or stable disease (SD), per RECIST v1.1, at any post-baseline visit until the first progressive disease (PD) or new anti-cancer therapy. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

According to RECIST 1.1, PFS was defined as the length of time from the initial infusion of study drug until the earliest date of disease progression, as determined by ICR, or death due to any cause, if occurring sooner than progression.

Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of retifanlimab and within 90 days of the last administration of retifanlimab.

Cmax was defined as the maximum observed plasma concentration.

tmax was defined as the time to the maximum concentration.

Cmin was defined as the minimum observed plasma concentration over the dose interval.

AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

Incyte Corporation

Treatment-emergent adverse events (TEAEs), defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab and within 90 days of the last administration of retifanlimab, have been reported.

Participants received retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W).

Retifanlimab 500 mg

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

The Full Analysis Set (FAS) included all participants enrolled in the study who received at least 1 dose of study drug.

Incyte Corporation Call Center (US)

Full Analysis Set: all participants enrolled in the study who received at least 1 dose of study drug

Objective Response Rate (ORR)

Full Analysis Set. All participants with confirmed tumor responses (CR or PR) by ICR according to RECIST v1.1 were analyzed. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method and Klein and Moeschberger's method with log-log transformation.

Duration of Response (DOR)

Full Analysis Set. Confidence intervals were calculated based on the exact method for binomial distributions.

Disease Control Rate (DCR)

Full Analysis Set. Median PFS time was estimated using the Kaplan-Meier method. The confidence interval for median PFS time was calculated using the method of Brookmeyer and Crowley.

Progression-free Survival (PFS)

Full Analysis Set. Median survival time was estimated using the Kaplan-Meier method. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.

Overall Survival

Safety Evaluable Population: all enrolled participants who received at least 1 dose of study drug

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Pharmacokinetic (PK) Evaluable Population: all participants who received at least 1 dose of study drug and provided a Baseline and at least 1 postdose serum sample (1 PK measurement)

Cmax of Retifanlimab

Tmax of Retifanlimab

Cmin of Retifanlimab

AUC0-t of Retifanlimab

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Squamous Cell Carcinoma of Head and Neck

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Head and Neck Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Pancreatic Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Camurati-Engelmann Disease

Pembrolizumab

Immune Checkpoint Inhibitors

Route: IV Infusion Frequency: QW Current Dose: 1500mg

Route: IV Infusion Frequency: Q3W Dose: 200mg

BCA101

David Bohr

Debanjali Ghosh

Assuntina Sacco, MD

Gino In, MD

Deborah Wong, MD

Hamza Elmohd

Jameel Muzaffar, MD

DFCI Clinical Trials Hotline

Glen Hanna, MD

Paul Paik, MD

CPDM Nurse Navigator

Sarah Brodeur

Dan Zanberg, MD

Lilli Neal

Carly Fecio

John Kaczmar, MD

Mike Gibson, MD

Beryl Tross

Van Morris, MD

Phillippe Bedard, MD

The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may exert synergistic activity in patients with EGFR-driven tumors.

This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A) followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101 plus pembrolizumab.

The study population in dose escalation (Part A) of single agent BCA101 consists of subjects with EGFR-driven advanced solid tumors refractory to standard of care or for whom no standard of care is available. Dose escalation (Part A) of combination BCA101 and pembrolizumab consists of subjects with either Squamous Cell Carcinoma of the Head and Neck (HNSCC) or Squamous Cell Carcinoma of the Anal Canal (SCCAC) whose tumors are refractory to standard of care or for whom no standard of care is available.

Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is determined, the study will continue with expansion cohorts (Part B) with select tumor types. Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma. Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC and 2) SCCAC.

Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors

First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-Driven Advanced Solid Tumors

Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.

Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST

Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST

Determine PFS in each part of the study, per RECIST v1.1 and iRECIST

Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST

Determine survival rates in each part of the study.

Incidence and titer of anti-drug-antibodies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nimotuzumab With Radiotherapy in the Treatment of Anal Canal Cancers	NCT01382745	Squamous Cell C...	Nimotuzumab Intensity Modul...	18 Years -	Sir Mortimer B. Davis - Jewish General Hospital
A Study of INCMGA00012 in Squamous Carcinoma of the Anal Canal Following Platinum-Based Chemotherapy (POD1UM-202)	NCT03597295	Squamous Cell C...	Retifanlimab	18 Years -	Incyte Corporation
A Study of INCMGA00012 in Squamous Carcinoma of the Anal Canal Following Platinum-Based Chemotherapy (POD1UM-202)	NCT03597295	Squamous Cell C...	Retifanlimab	18 Years -	Incyte Corporation
Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors	NCT04429542	Head and Neck S... Squamous Cell C... Colorectal Canc... Squamous Cell C... EGFR Amplificat... Epithelial Ovar... Pancreas Cancer Cutaneous Squam... Head and Neck N... Carcinoma, Squa... Squamous Cell C...	BCA101 Pembrolizumab	18 Years -	Bicara Therapeutics

Spots Global Cancer Trial Database for squamous cell carcinoma of anal canal