PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors

Study at a glance

From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors

ClinicalTrials.gov ID

NCT03284723

Acronym / sponsor ID

C0541001

Conditions

Breast Neoplasms

Keywords

HER2, PF-06804103, ADC, breast cancer, neoplasms, solid tumors, human epidermal growth receptor 2

Phase

Phase 1

Study type

Interventional

Recruitment status

TerminatedReason stopped: The trial was terminated based on the stage in drug development and assessment of PF-06804103 relative to the leading external competition. The decision was not due to a safety concern.

Enrolment

95 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

1 Nov 2017 (actual)

Primary completion

31 Aug 2021 (actual)

Study completion

31 Aug 2021 (actual)

First posted

15 Sep 2017 (actual)

Results

Posted 3 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

2

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A

   Time frame: First cycle, Day 1 up to Day 21

   A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose). (1) Hematologic: Grade 4 neutropenia lasting >7 days; febrile neutropenia; Grade >＝3 neutropenic infection; Grade >＝3 thrombocytopenia with bleeding; thrombocytopenia; (2) Non-hematologic: Grade >=3 toxicities that were considered clinically significant; delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting treatment related toxicities; concurrent AST or ALT >3x ULN and total bilirubin >2x ULN; any Grade 5 event.

2. Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B

   Time frame: First Cycle, Day 1 up to Day 28

   A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 28 days of first dose). (1) Hematologic: including a delay greater than 1 week in administration of the next scheduled dose of study treatment due to persistent treatment-related toxicities; Grade 4 neutropenia lasting >7 days; febrile neutropenia; Grade >=3 neutropenic infection; Grade >=3 thrombocytopenia with bleeding; thrombocytopenia. (2) Non-hematologic: including Grade >=3 toxicities that are considered clinically significant; Grade 3 QTc prolongation despite correction of reversible causes; delayed by >2 week in receiving the next scheduled dose of any study treatment due to persisting treatment-related toxicities; inability to administer at least 80% of the planned palbociclib or letrozole or 100% of the planned PF-06804103 doses during Cycle 1 due to toxicity related to the study treatment; concurrent AST or ALT >3x ULN and total bilirubin >2x ULN; any Grade 5 event.

3. Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs

   Time frame: From the first dose of study treatment up to a minimum of 28 calendar days after the last dose of study treatment (maximum duration between first and last dose: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as those with initial onset or increasing in severity after the first dose of study medication. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.

4. Number of Participants With Laboratory Abnormalities-Hematology

   Time frame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

   Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from <=Grade 2 at baseline to Grade 3 or above, including the following parameters: anemia, INR increased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased.

5. Number of Participants With Laboratory Abnormalities-Chemistries

   Time frame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

   Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from <=Grade 2 at baseline to Grade 3 or above, including the following parameters: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, hyperglycemia, hypermagnesemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased.

6. Number of Participants With Laboratory Abnormalities-Urinalysis

   Time frame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

   Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from <=Grade 2 at baseline to Grade 3 or above.

7. Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria

   Time frame: From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment), maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B

   Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in a supine or seated position.

8. Percentage of Participants With Objective Response in Part 2

   Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)

   Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

9. Duration of Response (DR) in Part 2

   Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)

   Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.

10. Progression-Free Survival (PFS) in Part 2

    Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)

    Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.

11. Time to Tumor Progression (TTP) in Part 2

    Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or withdrawal from treatment (maximum treatment duration: 49.4 weeks)

    Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 37420274Meric-Bernstam F, Calvo E, Lee KS, Moreno V, Park YH, Rha SY, Chalasani P, Zhong W, Zhou L, Pirie-Shepherd S, Leung ACF, Curigliano G. Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study. Mol Cancer Ther. 2023 Oct 2;22(10):1191-1203. doi: 10.1158/1535-7163.MCT-23-0101.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.
• Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

46 sites in 6 countries: see every site and its status.