A Phase 1 Study of PF-08046054/SGN-PDL1V in Advanced Solid Tumors
Study Identifier:
C5851001/SGNPDL1V-001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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Study Summary
To test the safety of a drug called SGN-PDL1V in participants with solid tumors. It will also study the side effects of this drug. Parts A and B of the study will find out how much SGN- PDL1V should be given to participants. Part C will use the dose found in Parts A and B to find out how safe SGN-PDL1V is and if it works to treat solid tumor cancers. To evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-PDL1V in pts with advanced solid tumors. To assess the safety/tolerability and antitumor activity of SGN-PDL1V, a novel investigational antibody-drug conjugate that delivers monomethyl auristatin E to cells that express Programmed Cell Death Ligand 1 (PDL1). Methods SGNPDL1V-001 (NCT05208762) is a phase 1 study enrolling patients (pts) with relapsed/refractory PDL1-expressing solid tumors (non-small cell lung cancer [NSCLC], head and neck squamous cell carcinoma [HNSCC], triple negative breast cancer [TNBC], and esophageal cancer [EC]) who progressed on standard of care therapies. Measurable disease per RECIST v1.1, and ECOG PS of ≤1 are required. In dose escalation, pts received doses of SGN-PDL1V from 0.5-1.75 mg/kg on days 1, and 8 of every 21-day cycle using adjusted ideal body weight. This study will evaluate the safety, tolerability, PK, and antitumor activity of PF-08046054 when administered as monotherapy in participants with advanced solid malignancies and as combination therapy in participants with metastatic or unresectable HNSCC or NSCLC.
To update response data by level of PDL1 expression.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I
Sex
Female & Male
Age
18 - 64 Years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Inclusion Criteria:
- Parts A and B:
- Participants must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor types
- Non-small cell lung cancer (NSCLC)
- Head and neck squamous cell carcinoma (HNSCC) (except nasopharyngeal cancer)
- Esophageal squamous cell carcinoma (SCC)
- Triple negative breast cancer (TNBC)
- Participants must have disease that is relapsed or refractory, that has progressed on approved therapies, be intolerant to or refused such therapies, or such and therapies are contraindicated and in the judgement of the investigator, should have no appropriate SoC therapeutic option
- Participants must have PD-L1 expression based on historical testing
- Part C:
- Participants must have disease that is relapsed or refractory or be intolerant to SoC therapies and must have one of the following tumor types
- HNSCC
- Participants with HNSCC must have histologically or cytologically-confirmed HNSCC
- NSCLC
- Participants must have histologically or cytologically-confirmed NSCLC. Participants with SCC and non--SCC histology are eligible. Note: Participants with a neuroendocrine component or histology are not eligible.
- Esophageal SCC
- Ovarian cancer
- Melanoma
- TNBC
- Gastric cancer
- Participants must have been previously tested for PD-L1 expression and should have PD-L1 expression ≥1 or <1 by CPS or TPS based on historical testing
- Part D and Part E:
- Participants must have histologically or cytologically-confirmed disease of the HNSCC or NSCLC
- Participants must have PD-L1 expression based on historical testing
- Participants with NSCLC; PD-L1 expression ≥ 1% by TPS
- Participants with HNSCC; PD--L1 expression ≥1 by CPS
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Measurable disease per RECIST v1.1 at baseline
- Patients (pts) with relapsed/refractory PDL1-expressing solid tumors (non-small cell lung cancer [NSCLC], head and neck squamous cell carcinoma [HNSCC], triple negative breast cancer [TNBC], and esophageal cancer [EC]) who progressed on standard of care therapies. Measurable disease per RECIST v1.1, and ECOG PS of ≤1 are required
- 1 Participants must provide written informed consent.
- 2 a. Dose Escalation (Part A) and Dose and Dosing Regimen Optimization (Part B): Participants must have histologically or cytologically confirmed metastatic or unresectable HNSCC (other than nasopharyngeal carcinoma), NSCLC, TNBC, or esophageal SCC. - Participants must have relapsed or refractory disease, progression, intolerance, or refusal of such therapy with approved therapies or contraindications to such therapy. -PD-L1 expression must be ≥ 1. - For participants with locally advanced/metastatic NSCLC, the presence of tumor genomic alterations for which approved targeted agents are available, including but not limited to EGFR mutations, ALK rearrangements, and ROS1 rearrangements, must be determined prior to enrollment. - Participants with such tumor genomic abnormalities must have received approved mutation-specific targeted therapy with PD. - Participants who do not have such tumor genomic alterations (with approved targeted agents) must have received anti-PD-1 or anti-PD-L1 (if available) therapy and platinum-containing two-agent chemotherapy dosing regimens (concurrent or sequential administration) and have progressed during these dosing regimens. - Participants with HNSCC must have received anti-PD-1 therapy (if available) and platinum-containing chemotherapy dosing regimens (concurrent or sequential administration) and have progressed during treatment with these dosing regimens, unless the use of this therapy is contraindicated or the participant is intolerant due to toxicity.
- 3 b. Dose Expansion (Part C): Participants must have relapsed or refractory disease or be intolerant to SoC therapy as described below, unless contraindicated: HNSCC； Regardless of PD-L1 expression. Must have histologically or cytologically confirmed HNSCC. - The primary tumor site must be the oral, oropharynx, hypopharynx, or larynx. - Must have received prior anti-PD-1 therapy (if applicable) and have received a platinum-containing chemotherapy dosing regimen (concurrent or sequential) with progression during treatment. No prior prior treatment with > 1st line cytotoxicity in a locally advanced or metastatic setting. -Provide results from previous PD-L1 expression assays. NSCLC； Regardless of PD-L1 expression Must have histologically or cytologically confirmed NSCLC (IIIB, IIIC, stage IV). - The presence of tumor genomic alterations for which an approved targeted drug is available, including but not limited to sensitizing EGFR mutations, ALK rearrangements, and ROS1 rearrangements, must be determined prior to enrollment. -Patients with tumor genomic alterations must have received no more than 2 approved mutation-specific targeted therapies with PD. Up to 1 line of anti-PD-L1 or anti-PD-1 therapy (concomitant or sequential with platinum-containing chemotherapy) may also be accepted. - Participants who do not have such tumor genomic alterations (with approved targeted agents) must have received anti-PD-1 or anti-PD-L1 therapy (if available) and platinum-containing chemotherapy dosing regimens (concurrent or sequential dosing) with progression/recurrence during treatment. Participants must not have received prior > 2nd line cytotoxic therapy. Participants who have progressed or relapsed ≤ 6 months after the last dose of platinum-containing therapy may be eligible for the study under adjuvant, neoadjuvant, or concomitant chemoradiotherapy regimens for early or locally advanced disease. - No prior prior treatment with > 1 line of cytotoxicity. Participants who have progressed or relapsed ≤ 6 months after the last dose of platinum-containing therapy may be eligible for the study under adjuvant, neoadjuvant, or concomitant chemoradiotherapy regimens for early or locally advanced disease. -Provide results from previous PD-L1 expression assays. Signal Exploration Cohort: - Participants with TNBC, ovarian cancer, esophageal SCC, gastric cancer, or melanoma. Must have relapsed or refractory disease, progression on approved therapies, intolerance or refusal of such therapy, or contraindications to such therapy, and the investigator judges that the participant has no suitable SoC options. Biology Cohort: - Participants who meet the above dose expansion criteria and have PD-L1 expression-negative NSCLC or HNSCC, TNBC, esophageal SCC, melanoma, gastric cancer, or ovarian cancer. - There is no specific number of participants for each tumor type. Must have an accessible tumor that can be tested for multiple (up to 3) fresh biopsies.
- 4 c. Co-dosing cohorts (Parts D and E): 1L HNSCC Participants must have histologically or cytologically confirmed HNSCC. The primary tumor site must be the oral, oropharynx, hypopharynx, or larynx. Participants must not have received anti-PD-1 or PD-L1 therapy or other immunotherapy agents for the tumor under investigation. Participants must have not received prior cytotoxic therapy in a locally advanced or metastatic setting. Cytotoxic therapy should only be used in the context of adjuvant/neoadjuvant therapy with progression or recurrence ≥ 6 months after the last dose. Participants must have PD-L1 expression ≥ 1 (as determined by previous CPS test results). 1L NSCLC： - Participants in the two-drug cohort must have prior local testing results demonstrating a tumor PD-L1 expression metric TPS of ≥1%. - Participants in the triple-drug cohort must have prior local testing results demonstrating a tumor PD-L1 expression metric TPS of < 50%. - Participants must have histologically or cytologically confirmed NSCLC. - Participants must not have known AGA (e.g., EGFR mutation, ALK translocation). Participants must not have received anti-PD-1 or PD-L1 therapy or other immunotherapy agents for the tumor under investigation. Participants must have not received prior cytotoxic therapy in a locally advanced or metastatic setting. Cytotoxic therapy should only be used in the context of adjuvant/neoadjuvant therapy with progression or recurrence ≥ 6 months after the last dose.
- 5 Be at least 18 years of age and be a legal adult at the time of signing informed consent
- 6 ECOG score of 0 or 1
- 7 Have measurable disease at baseline as per RECIST v1.1
- 8 Laboratory tests assess adequate kidney, liver, and bone marrow function
- 9 Female participants of childbearing potential, as well as male participants, agree to relevant contraceptive requirements
Exclusion criteria
- History of another malignancy within 3 years of first dose of study treatment or any evidence of residual disease from a previously diagnosed malignancy.
- Known active central nervous system metastases. Participants with previously-treated brain metastases may participate provided they:
- Are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment
- Have no new or enlarging brain metastases
- And are off of corticosteroids prescribed for symptoms associate with brain metastases for at least 7 days prior to first dose of study treatment
- Lepto-meningeal disease
- Prior treatment with an anti-PD-L1 agent within less than 5 half-lives. This duration of time will vary according to the half-life of the specific agent.
- Previous receipt of an monomethylauristatin E (MMAE)-containing agent.
- Pre-existing neuropathy ≥Grade 2 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
- 1History of other malignancies within 3 years prior to the first dose, with the exception of adequately treated carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
- 2Presence of known active central nervous system metastases
- 3Leptomeningeal disease
- 4Prior anti-PD-L1 therapy (when indicated as intended) within less than 5 half-lives
- 5Prior receipt of MMAE-containing medications
- 6Presence of ≥ grade 2 neuropathy according to NCI CTCAE v5.0
- 7Active viral, bacterial, or fungal infection of any grade (per NCI CTCAE version 5.0) within 2 weeks prior to the first dose
- 8Presence of known or suspected autoimmune disease, or significant autoimmune-related toxicity from prior tumor immunotherapy, that is currently active, has not completely resolved, or is at risk of recurrence
- 9Uncontrolled diabetes mellitus
- 10Known positive expression of hepatitis B surface antigen. Known to have active hepatitis C infection
- 11Known positive for human immunodeficiency virus (HIV).
- 12History of cerebrovascular events (stroke or transient ischemic attack), unstable angina, myocardial infarction, congestive heart failure, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to the first dose
- 13History of non-infectious ILD or lung inflammation requiring steroid therapy, current presence of ILD or lung inflammation, ≥ grade 3 lung disease unrelated to the underlying malignancy, pulmonary radiation therapy of > 30Gy within 6 months prior to the first dose of study treatment, and known diffusing capacity for pulmonary carbon monoxide [DLCO] adjusted for hemoglobin <50% predicted. Participants with chronic obstructive pulmonary disease (COPD) are eligible for the study, provided supplemental oxygen or systemic corticosteroids (> 10 mg/day prednisone or equivalent) are not required
- 14Receipt of a potent inducer or inhibitor of CYP3A within 14 days prior to the first dose
- 15Not completed chemotherapy, immunotherapy, biologics, and/or other approved or investigational antineoplastic therapy within 4 weeks prior to the first dose (when indicated as protocol), or within 2 weeks prior to the first dose of PF-08046054 (if disease progression occurs during treatment)
- 16No completion of focal radiotherapy or major surgery within 2 weeks prior to the first dose
- 17Participants who are breastfeeding, pregnant, or planning to become pregnant between informed and 2 months/4 months after the end of the last dose
- 18Known hypersensitivity to any excipients contained in the study drug
- 19Investigator estimated life expectancy < 12 weeks
- 20Live vaccine within 30 days prior to the first dose
- 21Has other serious underlying medical condition that, in the opinion of the investigator, would impair the participant's ability to receive or tolerate planned treatment and follow-up
- 22Any toxicity associated with prior therapy that has not returned to baseline or > Grade 1, with the exception of alopecia
- 23For Parts C, D and E, diagnosed immunodeficiency or receiving long-term systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment intervention. Has an active autoimmune disease requiring systemic therapy within the past 2 years
- 24Study site staff and their family members who are directly involved in the conduct of the study, site staff who are otherwise supervised by the investigator, and sponsor and sponsor representatives who are directly involved in the conduct of this study and their families
- 25Presence of any abnormality in physical examination or laboratory tests that may increase the risk to the study participant or that, in the judgment of the investigator, may make the participant unsuitable for participation in the study
- 26Any medical or psychiatric condition that may increase the risk to the study participant or (in the judgment of the investigator) may make the participant unsuitable for participation in the study, including recent (within the past year) or current suicidal thoughts/behaviors or abnormal laboratory tests
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Emiliano Calvo
Status
Recruiting
Condition(s) Treated at Site
Solid Tumor
Non-Small Cell Lung Cancer
HNSCC
Esophageal
Breast Cancers
Gastric
Endometrial
Pancreas
Liver
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Amita Patnaik
Status
Recruiting
Condition(s) Treated at Site
Solid Tumor
Non-Small Cell Lung Cancer
HNSCC
Esophageal
Breast Cancers
Gastric
Endometrial
Pancreas
Liver
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Justin Call
Status
Recruiting
Condition(s) Treated at Site
Solid Tumor
Non-Small Cell Lung Cancer
HNSCC
Esophageal
Breast Cancers
Gastric
Endometrial
Pancreas
Liver