Cemiplimab and ISA101b Vaccine in Adult Participants With Recurrent/Metastatic Human Papillomavirus (HPV)16 Cervical Cancer Who Have Experienced Disease Progression After First Line Chemotherapy

A Phase 2 Study of Cemiplimab, an Anti-PD-1 Monoclonal Antibody, and ISA101b Vaccine in Patients With Recurrent/Metastatic HPV16 Cervical Cancer Who Have Experienced Disease Progression After First Line Chemotherapy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04646005

Enrollment

113

Registered

2020-11-27

Start date

2021-06-28

Completion date

2024-05-29

Last updated

2025-09-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cervical Cancer

Keywords

HPV16 positive, Squamous histology, Recurrent, Metastatic, Adenocarcinoma/adenosquamous histology

Brief summary

The primary objective of the study is to estimate the clinical benefit of cemiplimab + ISA101b after progression on first line chemotherapy, as assessed by objective response rate (ORR). The secondary objectives of the study are: * To characterize the safety profile of cemiplimab + ISA101b * To assess preliminary efficacy of cemiplimab + ISA101b as measured by duration of response (DOR), progression-free survival (PFS), and overall survival (OS)

Interventions

DRUGCemiplimab

Administered intravenously (IV) every three weeks (Q3W)

BIOLOGICALISA101b

Administered by subcutaneous (SC) injection on day 1, day 29, and day 50

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: 1. Adult patients ≥18 years of age (or the legal age of adults to consent to participate in a clinical study per country specific regulations). 2. Has histologically confirmed recurrent or metastatic HPV16 positive cervical cancer as determined by an investigational HPV16 PCR assay, who have experienced disease progression after treatment with platinum containing therapy as defined in the protocol 3. Patient must be determined to be positive for HPV16 genotype, as determined by a specified central reference laboratory. 4. Patient must have measurable disease as defined by RECIST 1.1. 5. Must have received prior bevacizumab and taxol unless meets pre-specified protocol criteria 6. ECOG performance status of 0 or 1. 7. Has adequate organ and bone marrow function as defined in the protocol. 8. Anticipated life expectancy ≥20 weeks. Key

Exclusion criteria

1. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway. 2. Prior treatment with other systemic immune-modulating agents as defined in the protocol 3. Major surgery or radiation therapy within 14 days of first administration of study drug 4. Has received treatment with an approved systemic therapy within 4 weeks of first dose of study drug, or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities except for laboratory changes as described in the protocol 5. Has another malignancy that is progressing or requires active treatment and/or history of malignancy other than cervical cancer within 3 years of date of first planned dose of study drug as defined in the protocol 6. Has any condition that requires ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 4 weeks prior to the first dose of study drug. 7. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol NOTE: Other protocol-defined Inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (ORR)	From enrollment to last dose (~up to 23 months)	Objective response rate (ORR) is determined by the proportion of participants with best overall response of complete response (CR) or partial response (PR) in the Full analysis set (FAS).

Secondary

Measure	Time frame	Description
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs)	From enrollment to last dose (~up to 23 months)	—
Number of Participants With Any Treatment Emergent Adverse Events of Special Interest (TE AESIs)	From enrollment to last dose (~up to 23 months)	—
Number of Participants With Any Serious TEAE	From enrollment to last dose (~up to 23 months)	—
Number of Participants With at Least One Lab Abnormality	From enrollment to last dose (~up to 23 months)	—
Number of Treatment Emergent Adverse Events (TEAEs)	From enrollment to last dose (~up to 23 months)	Treatment-emergent AEs (TEAEs) are defined as AEs that developed or worsened during the on-treatment period and treatment-related AEs that occur during post-treatment period.
Duration of Response (DOR)	From enrollment to last dose (~up to 23 months)	—
Progression Free Survival (PFS)	From enrollment to last dose (~up to 23 months)	—
Overall Survival (OS)	From enrollment to last dose (~up to 23 months)	—
Number of Participants With at Least One Lab Abnormality With Severity of ≥ Grade 3	From enrollment to last dose (~up to 23 months)	Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Countries

Belgium, Brazil, Italy, Netherlands, Russia, South Korea, Spain, United States

Participant flow

Pre-assignment details

229 participants were screened, and of these, 113 were enrolled and 116 were screen failures.

Participants by arm

Arm	Count
ISA 101b + Cemiplimab 350 mg Q3W A dose of 100 μg/peptide ISA101b on days 1, 29, and 50 (total of 3 doses). Cemiplimab 350 mg (milligrams) given by IV (intravenous) infusion over 30 minutes Q3W (every 3 weeks) on days 8 and 29 in cycle 1, on days 1 and 22 in cycles 2 through 4, and on days 1, 22, and 43 in all subsequent cycles until disease progression or discontinuation of study drug	113
Total	113

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Death	20
Overall Study	Progressive Disease	71
Overall Study	Sponsor Request	9
Overall Study	Withdrawal by Subject	12

Baseline characteristics

Characteristic	ISA 101b + Cemiplimab 350 mg Q3W
Age, Continuous	49.4 Years STANDARD_DEVIATION 11.96
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	88 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	14 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	91 Participants
Sex: Female, Male Female	113 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	68 / 113
other Total, other adverse events	99 / 113
serious Total, serious adverse events	34 / 113

Outcome results

Primary

Objective Response Rate (ORR)

Objective response rate (ORR) is determined by the proportion of participants with best overall response of complete response (CR) or partial response (PR) in the Full analysis set (FAS).