| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced solid tumors and non-Hodgkin lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced solid tumors and non-Hodgkin lymphoma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065147 |
| E.1.2 | Term | Malignant solid tumor |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10012818 |
| E.1.2 | Term | Diffuse large B-cell lymphoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- Part 1:To evaluate the efficacy of NIR178 and PDR001 combination in patients with selected advanced solid tumors and diffuse large B cell lymphoma (DLBCL)
- Part 2: To assess the efficacy of Continous and several intermittent dosing schedules of NIR178 in combination with PDR001 in NSCLC
- Part 3: To evaluate efficacy of the best performing dosing schedule of NIR178 in one or two selected tumor type from part 1 and part 2 |
|
| E.2.2 | Secondary objectives of the trial |
- To assess efficacy of NIR178+PDR001 in select advanced solid tumors and lymphoma
- To assess the safety and tolerability of the NIR178 and PDR001 combination
- To characterize changes in the immune infiltrate in tumors
- To characterize the pharmacokinetics (PK) of NIR178, its metabolite NJI765 and PDR001 in combination
- To assess immunogenicity of PDR001
- Japanese Safety Run-in: To assess the preliminary safety, and PK of
single agent NIR178 and in combination with PDR001 in Japanese patients |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Histologically documented advanced or metastatic solid tumors or
lymphomas
a.Part 1: 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.Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC.For those with mixed histology, there must be a predominant histology
c.Part 3: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 a
candidate 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 platinum containing 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 must have received prior BRAF V600E inhibitor therapy, either single-agent or in combination with a MEK inhibitor
• mCRPC:
-Of the 1-3 prior lines of therapy, patients must have received and failed at least one line of treatment after emergence of castration resistant disease
• DLBCL:
-Patients with DLBCL should be limited to those with no available
therapies of proven clinical benefit
-Patient should have had prior autologous hematopoietic stem cell
transplantation or determined to be ineligible for auto-HSCT
• NSCLC:
-Patients with NSCLC must have received a prior platinum-based
combination
-For patients with NSCLC, EGFR mutation with exon 19 deletion or L858R mutation(Exon 21)or anaplastic lymphoma receptor tyrosine
kinase(ALK) rearrangement positive must have failed prior TKI therapy
-Patients with EGFR positive NSCLC with a T790M mutation must have
progressed on osimertinib or discontinued due to toxicity
-If one of the tumor groups selected for part 3 is NSCLC, this group will
enroll patients previously exposed to immunotherapy
4 Patients must not have received prior immunotherapy(previous
immune checkpoint inhibitors; single agent and/or combination therapy with anti-CTLA-4, anti-PD-1, anti-PD-L1), except cutanous melanoma, I/O pre-treated
5 Patients must have measurable disease as >20 mm with conventional techniques or as >10 mm with spiral computer tomography(CT) scan,MRI, or calipers by clinical exam
Other protocol defined inclusion criteria may apply |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At protocol define timepoints until End of study. |
|
| E.5.2 | Secondary end point(s) |
- ORR, DCR, DoR, PFS, 2 years Overall Survival rate
- Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters. Dose interruptions, reductions and dose intensity.
- Change from baseline in TILs
- Plasma concentration time profiles of NIR178, NJI765 and PK parameters. Serum concentration time profiles of PDR001 and PK parameters.
- Presence and/or concentration of anti-PDR001 antibodies
- Frequency, severity and seriousness of DLTsl AEs, laboratory
abnormalities and other safety parameters. Plasma concentration time
profiles of NIR178 and PK parameters. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At protocol define timepoints until End of study. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Japan |
| Singapore |
| Taiwan |
| United States |
| Switzerland |
| Austria |
| Belgium |
| Czechia |
| France |
| Germany |
| Italy |
| Netherlands |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study will end when all patients have completed the treatment period and 150-day safety follow-up, and at least 80% of patients have completed at least 24 months of survival follow up from start of study therapy. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 30 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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