Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566

Pfizer

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: PF-04518600 plus PF-05082566; Drug: PF-04518600

Study type: Interventional

Funder types: Industry

Identifiers

NCT02315066

2014-004107-75 (EudraCT Number)

OX40 (Other Identifier)

B0601002 (Other Identifier)

Details and patient eligibility

About

To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Enrollment: 174 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
• Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed.
• Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
• Part B2

Arm 1 only:

1. Ocular melanoma patients with advanced/metastatic disease, or
2. Cutaneous/acral melanoma patients with advanced/metastatic disease who have received checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which disease progressed. [Note: Checkpoint inhibitor may have been part of a combination therapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Any questions on prior treatment may be discussed with the Sponsor.

Arm 2 only:

• Histological or cytological diagnosis of NSCLC with advanced/metastatic disease. Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which disease progressed. [Note: Previous anti PD L1 or anti PD 1 mAb may have been part of a combination therapy, eg, in combination with chemotherapy, as long as the combination did not contain OX40 or 4 1BB agonist.]
• Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function

Exclusion criteria

• Brain metastases requiring steroids
• Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
• Active and clinically significant bacterial, fungal, or viral infection
• History of active autoimmune disorders
• History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
• Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
• Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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174 participants in 2 patient groups

PF-04518600

Experimental group

Description:

OX40 agonist

Treatment:

Drug: PF-04518600

Drug: PF-04518600

PF-04518600 plus PF-05082566

Experimental group

Description:

OX40 (CD134) agonist plus 4-1BB (CD137) agonist

Treatment:

Drug: PF-04518600 plus PF-05082566

Drug: PF-04518600 plus PF-05082566