Phase 2
Completed N=26
GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors
Neoplasms
Source: ClinicalTrials.gov NCT03693612 ↗
Enrolled (actual)
26
Serious AEs
46.2%
Results posted
Aug 2022
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1 — 0; 0; 0; 0 Participants
Summary
The purpose of this study is to evaluate if the combination of GSK3359609 and tremelimumab is safe and tolerable (Part 1) and provides significant survival benefit to subjects with relapsed/refractory (R/R) Head and Neck Squamous Cell Carcinomas (HNSCC) to warrant further clinical investigation (Part 2). Part 1 (dose escalation) will enroll subjects with advanced, selected solid tumors. Subjects will receive escalating doses of GSK3359609 and tremelimumab in combination in Part 1. Part 2 is randomized expansion and will enroll subjects with R/R HNSCC who have disease progression after receiving at least 1 platinum-based chemotherapy and at least 1 anti-programmed death receptor protein-1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) therapy, whether in combination or separately. In Part 2, subjects will be randomized in a ratio of 2:1 to receive either GSK3359609 in combination with tremelimumab at the recommended Phase 2 dose or investigators choice of a single-agent standard of care (SOC) therapy including paclitaxel, docetaxel or cetuximab. The total duration of subjects in the study will be approximately 4 years.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1 |
0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With DLTs According to Severity-Part 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1 |
1; 1; 5; 3; 16; 0 | — |
| PRIMARY Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1 |
0; 0; 0; 0; 4; 1 | — |
| PRIMARY Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1 |
104; 128; 128; 133.67; 127.5; 16 | — |
| PRIMARY Change From Baseline in Temperature-Part 1 |
36.5; 36.9; 36.8; 36.6; 36.64; 0 | — |
| PRIMARY Change From Baseline in Pulse Rate-Part 1 |
81; 83; 91.6; 79.67; 76.56; 1 | — |
| PRIMARY Change From Baseline in Respiratory Rate-Part 1 |
18; 18; 17.6; 16; 16.75; 0 | — |
| PRIMARY Change From Baseline in Oxygen Saturation-Part 1 |
96; 95; 95.6; 96; 97.63; 2 | — |
| PRIMARY Number of Participants With Electrocardiogram (ECG) Findings |
1; 1; 1; 1; 6; 0 | — |
| PRIMARY Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1 |
0.00; 0.00; 0.05; 0.01; 0.039; 0.00 | — |
| PRIMARY Change From Baseline in Hemoglobin Level-Part 1 |
125; 134; 123.4; 125; 111.5; 5 | — |
| PRIMARY Change From Baseline in Hematocrit Level-Part 1 |
0.38; 0.4; 0.385; 0.3937; 0.3421; 0 | — |
| PRIMARY Change From Baseline in Erythrocytes Count-Part 1 |
4.2; 4.65; 4.328; 4.673; 3.76; 0.13 | — |
| PRIMARY Change From Baseline in Albumin and Total Protein Levels-Part 1 |
41; 40; 36; 36.7; 37.9; 0 | — |
| PRIMARY Change From Baseline in Creatinine and Bilirubin Levels-Part 1 |
5; 7; 6.1; 6.1; 6.5; -1 | — |
| PRIMARY Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1 |
53; 68; 307.4; 121.5; 120.2; 2 | — |
| PRIMARY Change From Baseline in Amylase and Lipase Levels-Part 1 |
48; 50; 50.2; 40; 51.5; -2 | — |
| PRIMARY Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1 |
6.7; 7.3; 6.09; 5.897; 6.397; -0.3 | — |
| PRIMARY Change From Baseline in Specific Gravity of Urine-Part 1 |
1.015; 1.02; 1.0204; 1.021; 1.0159; 0.005 | — |
| PRIMARY Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1 |
6.5; 7; 6; 5.33; 6.16; -0.5 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Parameters-Part 1 |
0; 1; 0; 2; 0; 1 | — |
| PRIMARY Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1 |
0.79; 1.22; 1.856; 1.463; 2.211; -0.87 | — |
| PRIMARY Change From Baseline in Free Triiodothyronine (T3)-Part 1 |
3.5; 3.6; 2.75; 4.47; 3.88 | — |
| PRIMARY Change From Baseline in Free Thyroxine (T4)-Part 1 |
10; 11; 12.43; 13.84; 15.98; 2.57 | — |
| PRIMARY Overall Survival-Part 2 |
— | — |
| SECONDARY Overall Response Rate-Part 1 |
0; 0; 0; 0; 6.3 | — |
| SECONDARY Overall Response Rate-Part 2 |
— | — |
| SECONDARY Disease Control Rate-Part 1 |
0; 0; 0; 33.3; 12.5 | — |
| SECONDARY Disease Control Rate-Part 2 |
— | — |
| SECONDARY Progression Free Survival-Part 2 |
— | — |
| SECONDARY Time to Response-Part 2 |
— | — |
| SECONDARY Duration of Response-Part 2 |
— | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1 |
2758; 5965; 2686.6; 28340.9; 6098.3 | — |
| SECONDARY Cmax of Tremelimumab-Part 1 |
0; 0; 112312.1; 93206.7 | — |
| SECONDARY Cmax of Feladilimab-Part 2 |
— | — |
| SECONDARY Cmax of Tremelimumab-Part 2 |
— | — |
| SECONDARY Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1 |
462; 348; 3197; 856.4 | — |
| SECONDARY Cmin of Tremelimumab-Part 1 |
6467; 22466.3; 5715.6; 15084.9 | — |
| SECONDARY Cmin of Feladilimab-Part 2 |
— | — |
| SECONDARY Cmin of Tremelimumab-Part 2 |
— | — |
| SECONDARY Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1 |
545097.4; 453561.5; 4552653.1; 1055659.5 | — |
| SECONDARY AUC(0-t) of Tremelimumab-Part 1 |
18160725.7 | — |
| SECONDARY AUC(0-t) of Feladilimab-Part 2 |
— | — |
| SECONDARY AUC(0-t) of Tremelimumab-Part 2 |
— | — |
| SECONDARY Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1 |
0; 0; 1; 0; 5; 0 | — |
| SECONDARY Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 2 |
— | — |
| SECONDARY Change From Baseline in Free T4-Part 2 |
— | — |
| SECONDARY Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 2 |
— | — |
| SECONDARY Number of Participants With AEs, SAEs and AESI-Part 2 |
— | — |
| SECONDARY Number of Participants With AEs, SAEs, AESIs Based on Severity-Part 2 |
— | — |
| SECONDARY Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 2 |
— | — |
| SECONDARY Change From Baseline in SBP and DBP-Part 2 |
— | — |
| SECONDARY Change From Baseline in Temperature-Part 2 |
— | — |
| SECONDARY Change From Baseline in Pulse Rate-Part 2 |
— | — |
| SECONDARY Change From Baseline in Respiratory Rate-Part 2 |
— | — |
| SECONDARY Change From Baseline in Oxygen Saturation-Part 2 |
— | — |
| SECONDARY Change From Baseline in ECG Measurement-Part 2 |
— | — |
| SECONDARY Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 2 |
— | — |
| SECONDARY Change From Baseline in Hemoglobin Level-Part 2 |
— | — |
| SECONDARY Change From Baseline in Hematocrit Level-Part 2 |
— | — |
| SECONDARY Change From Baseline in Erythrocytes Count-Part 2 |
— | — |
| SECONDARY Change From Baseline in Albumin and Total Protein Levels-Part 2 |
— | — |
| SECONDARY Change From Baseline in Creatinine and Bilirubin Levels-Part 2 |
— | — |
| SECONDARY Change From Baseline in ALT, AST, ALP, LDH Levels-Part 2 |
— | — |
| SECONDARY Change From Baseline in Amylase and Lipase Levels-Part 2 |
— | — |
| SECONDARY Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels -Part 2 |
— | — |
| SECONDARY Change From Baseline in Specific Gravity of Urine-Part 2 |
— | — |
| SECONDARY Change From Baseline in pH of Urine-Part 2 |
— | — |
| SECONDARY Number of Participants With Abnormal Urinalysis Parameters-Part 2 |
— | — |
| SECONDARY Change From Baseline in TSH-Part 2 |
— | — |
| SECONDARY Change From Baseline in Free T3-Part 2 |
— | — |
Eligibility Criteria
Inclusion Criteria
- Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
- Male or female, aged 18 years or older.
- Body weight >=30 kilograms (kg).
- Histological or cytological documentation of an invasive malignancy that was diagnosed as locally advanced/metastatic or relapsed/refractory and is of one of the following tumor types: a) Part 1: cutaneous melanoma; HNSCC (oral cavity, larynx, oropharynx, hypopharynx, nasal cavity/paranasal sinuses); non-small cell lung cancer (squamous and non-squamous); urothelial carcinoma of the upper and lower urinary tract; clear cell renal carcinoma; castrate resistant prostate adenocarcinoma. b) Part 2: HNSCC (oral cavity, larynx, pharynx, paranasal sinuses).
- Part 1 only: Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists, or where standard therapy is refused. May be anti-PD-1/anti-PD-L1 experienced or naïve.
- Part 2 only: Disease that has progressed after receiving platinum-based chemotherapy (unless medically contraindicated or discontinued due to toxicity) and anti-PD-1/anti-PD-L1 therapy (in combination or as separate lines of therapy in either sequence).
- Measurable disease per RECIST version 1.1 guidelines. Palpable lesions that are not measurable by radiographic or photographic evaluations may not be utilized as the only measurable lesion. Any measurable lesion biopsied at Screening cannot be followed as a target/index lesion unless agreed upon by GlaxoSmithKline (GSK).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
- Adequate organ function.
- A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions apply: a) Not a woman of childbearing potential (WOCBP); or, b) A WOCBP who agrees to follow the contraceptive while receiving study intervention and for at least 180 days after the last dose of study intervention.
- A male subject must agree to use a highly effective contraception while receiving study intervention and for at least 180 days after the last dose of study intervention and refrain from donating sperm during this period.
- Agree to collection of tumor tissue: a) Part 1 and Part 2: Archival tumor tissue collected any time from the initial diagnosis of invasive malignancy; a fresh tumor biopsy will be required if archival specimen is unavailable prior to first dose. b) Part 1 pharmacokinetic/pharmacodynamic cohort(s): Archival tissue as noted in point (a) above. Paired tumor biopsies: tumor tissue collected any time after completion of dosing of the last therapy and prior to first dose and an on-treatment biopsy. c) Part 2: A minimum of 15 subjects from each arm will be required to provide paired tumor biopsies (in addition to the archival tissues as noted in point (a) above): tumor tissue collected any time after completion of dosing of the last therapy and prior to first dose and an on-treatment biopsy.
Exclusion Criteria
- Received prior treatment with the following therapies; calculation is based on date of last therapy to date of first dose of study intervention or SOC: a) Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4 [including tremelimumab] or Inducible T Cell Co-Stimulator (ICOS)-directed therapies at any time; b) >=4 lines of prior anticancer treatment: In subjects that relapse or progress within 1 year from the beginning of adjuvant or concurrent therapy, the adjuvant/concurrent therapy is considered first line therapy; c) Systemic anticancer therapy or investigational therapy within 30 days, or 5 half-lives, whichever is shorter; at least 14 days must have elapsed between the date of the last prior therapy to the date of first dose of study interven
Data sourced from ClinicalTrials.gov (NCT03693612). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.