Study of efficacy and safety of NIR178 and PDR001 combination in patients with selected solid tumors and non-Hodgkin lymphoma

Phase 1

• Conditions: Advanced solid tumors and non-Hodgkin lymphoma; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000241-49-BE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-14
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 416

Inclusion Criteria

1.Histologically documented advanced or metastatic solid tumors or lymphomas
a.Part1: renal cell carcinoma (RCC), pancreatic cancer, urothelial cancer, head and neck squamous cell carcinoma (HNSCC), diffuse large B-cell lymphoma (DLBCL), microsatellite stable colorectal cancer (MSS CRC), triple negative breast cancer (TNBC) melanoma or mCRPC
b.Part2: histologically confirmed diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant
histology
c.Part3: histologically confirmed diagnosis of advanced/metastatic malignancies should Part 3 be opened to enrollment. As of protocol
amendment 6, Part 3 will be opened to further assess TNBC patients with a PD-L1 SP-142 IC score of 0 (<1%). A second tumor group will be
considered for Part 3 after completion of Part 1
2.Patient must have a site of disease amenable to biopsy and be acandidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and again during therapy
3.Patients (other than those with DLBCL) must previously have received at least 1 and no more than 3 prior lines of therapy for their disease:
• MSS CRC:
-Patients with MSS CRC must have received (or be intolerant to) prior therapy with fluoropyrimidine-oxaliplatin- and irinotecan- based regimens
-Patient with wt RAS must have received prior treatment with an antibody targeting EGFR (e.g. cetuximab or panitumumab)
• TNBC:
Part 1:
-Patients with TNBC must have received a prior taxane- containing regimen
Part 3:
-Patients should have documented disease progression following, or intolerance to, no more than 2 prior lines of chemotherapy for advanced
or metastatic disease. Neoadjuvant and/or adjuvant chemotherapy administered with curative intent will count as one prior line of therapy, if disease recurred within 12 months of the last treatment
-Patients must have received prior systemic treatment that included taxane-based chemotherapy for (neo) adjuvant or metastatic disease
-Patients should have a known PD-L1 status as per local available testing determined by VENTANA PD-L1 SP142 Assay with IC score of 0 (<1%)
• Urothelial Cancer:
-Patients with urothelial cancer must have received a prior platinumcontaining regimen or be ineligible for cisplatin
• RCC:
-IO Naive: Patients with RCC must have received a prior VEGF tyrosine kinase inhibitor (TKI)
-IO pre-treated:Patients with RCC with no more than 2 prior lines of therapy. Patient must have received a prior VEGF TKI and have been
pretreated with an anti-PD-1/PD-L1 as a single agent or in combination
• HNSCC:
-I/O Naive: Patients with HNSCC with no more than 3 prior lines of therapy; must have received a prior platinum-containing regimen and have not been previously treated with any anti-PD1/L1 agents in single agent/combinations
-I/O pre-treated: Patients with HNSCC with no more than 2 prior lines of therapy; must have received a prior platinum-containing regimen and
have been pretreated with an anti-PD-1/PD-L1 as a single agent or in combinations
• Cutaneous Melanoma
-Patients must previously have received at least 1 and no more than 2 prior lines of therapy
-BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy
-BRAF V600E mutant patients: must have received prior anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. In addition,
subjects mu

Exclusion Criteria

- Ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR inhibitors for non-oncologic indications (e.g. Parkinson’s disease) may be considered for enrollment on a case by case basis.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of PDR001, with the exception of intranasal/inhaled corticosteroids or systemic corticosteroids at physiological doses (not exceeding equivalent of 10 mg/day of prednisone)
- History of interstitial lung disease or non-infectious pneumonitis
- History of another primary malignancy except for:
. Malignancy treated with curative intent and with no known active disease =2 years before the first dose of study drug and of low potential risk for recurrence
. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
. Adequately treated carcinoma in situ without evidence of disease
- Active or prior documented autoimmune disease within the past 2 years. Patients with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- More than 2 or 3 prior lines of therapy as indicated for each tumor type in the inclusion criteria 4
- Participation in another clinical study with an investigational product during the last 21 days prior to starting on treatment.

Other protocol defined exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified