Trial of PRO1160 (GEN1160) in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) (PRO1160-001)

Dose Escalation: Key Inclusion Criteria:

• All participants must have pathologically confirmed diagnosis of one of thefollowing tumor types:

• Metastatic RCC, including clear cell renal cell carcinoma (ccRCC) or papillaryRCC

• Metastatic or relapsed Epstein Barr virus (EBV)-associated NPC not amenable tofurther local therapies (EBV association may have been determined by testing ontumor tissue or peripheral blood)

• Advanced (Stage III or IV) NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) requiring systemic therapy, and mantle celllymphoma (MCL)

• Participants must have relapsed or refractory disease following prior systemictherapies known to confer clinical benefit. At minimum, participants should havereceived the following therapies (unless deemed ineligible, refused by theparticipant, or not available in the region):

• Participants with RCC must have received a minimum of one prior treatmentregimen, and have received a tyrosine kinase inhibitor (TKI) and a programmedcell death (ligand) ([PD[L)])-1 inhibitor

• Participants with EBV-associated NPC must have received a minimum of one priortreatment regimen, which must include a platinum-based chemotherapy regimen

• Participants with DLBCL must have received a minimum of 2 prior treatmentregimens, including a multi-agent chemoimmunotherapy regimen given withcurative intent (eg, rituximab, cyclophosphamide, doxorubicin, vincristine, andprednisone [R-CHOP]), and participants must have received intensive salvagechemotherapy with hematopoietic stem cell transplant (HSCT) if consideredeligible by the investigator

• Participants with FL must have received a minimum of 2 prior treatmentregimens, which must include a multi-agent chemoimmunotherapy regimen includingan anti-CD20 agent

• Participants with mantle cell lymphoma (MCL) must have received a minimum of 2prior treatment regimens, which must include a multi-agent chemoimmunotherapyregimen including an anti-CD20 agent

• Measurable disease at baseline:

• Participants with RCC and NPC must have measurable disease as defined perResponse Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (Eisenhaueret al., 2009)

• Participants with NHL must have measurable disease as defined by the LuganoClassification (Cheson et al., 2014)

• Participants must be willing to provide a pre-treatment tumor specimen (archival or new tissue biopsy samples). If a new tissue biopsy is required,procedures more invasive than a core biopsy or significant risk procedures forwhich the procedure-associated absolute risk of mortality or major morbidity inthe participant's clinical setting and specific institution is 2% or higher,should not be utilized.

Dose Escalation Key Exclusion Criteria:

• Prior treatment with anti-CD70 directed therapy

• Prior therapy with an antibody-drug conjugate (ADC) with a topoisomerase 1 inhibitorpayload

• Prior allogeneic hematopoietic stem cell transplant (HSCT). Participants with priorautologous HSCT must have completed the procedure at least 100 days prior to thefirst dose of study drug.

• Known active central nervous system metastases, including carcinomatous meningitis.Participants with brain metastases may participate provided the metastases have beentreated and are stable for at least 4 weeks prior to the first dose of study drug,they have no new or enlarging brain metastases and have discontinued corticosteroidsprescribed for symptoms associated with brain metastases for at least 7 days priorto the first dose of study drug. Participants with a history of brain metastases,suspected new brain metastases, or a diagnosis of RCC should have a magneticresonance imaging (MRI) of the brain at screening.

Expansion: Key Inclusion Criteria:

• Has pathological diagnosis of DLBCL, not otherwise specified (NOS) as defined by theWorld Health Organization (WHO) 2016 classification including both de novo orhistologically transformed.

• Has relapsed or refractory disease with no available standard therapy or is not acandidate for available standard therapy, and for whom, in the opinion of theinvestigator, experimental therapy with GEN1160 may be beneficial. Participant musthave received at least 2 systemic treatment regimens including CD20-containingchemoimmunotherapy.

• Has measurable disease according to the 2014 Lugano criteria (Cheson et al., 2014):

• A fluorodeoxyglucose (FDG)-positron emission tomography (PET) scandemonstrating positive lesion compatible with computed tomography (CT)- orMRI-defined anatomical tumor sites; AND

• A CT scan (or MRI) with involvement of ≥ 1 measurable nodal lesion (long axis > 1.5 centimeters (cm) and short axis > 1.0 cm) and/or ≥ 1 measurable extranodallesion (long axis > 1.0 cm).

• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

• Has a fresh biopsy (if clinically feasible and not considered as a high-riskprocedure) or an archival tumor biopsy and submit to the central laboratory for CD70assay

• Has acceptable laboratory test results per protocol

Expansion: Key Exclusion Criteria:

• Primary central nervous system (CNS) tumor or known CNS involvement.

• Has been exposed to any of the following prior therapies within the specifiedtimeframes:

• Received prior investigational CD70-targeting therapy, eg, CD70-directedchimeric antigen receptor T-cell (CAR-T) therapy, anti-CD70 monoclonal antibody (mAb), CD3 x CD70 bispecific monoclonal antibody (bsAb), or CD70 antibody-drugconjugate.

• Autologous stem cell transplant within 60 days prior to the first dose ofGEN1160.

• Allogeneic stem cell transplant within 90 days prior to the first dose ofGEN1160.

• Chemotherapy within 2 weeks or major surgery within 4 weeks of the first doseof GEN1160.

• Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeksprior to the first dose of GEN1160.

• Treatment with an investigational drug within 4 weeks or 5 half-lives of thedrug, whichever is shorter, prior to the first dose of GEN1160 or currentlyreceiving any other investigational agents.

• Prior treatment with live, attenuated vaccines within 30 days prior to thefirst dose of GEN1160. Examples of live vaccines include, but are not limitedto, the following: measles, mumps, rubella, varicella/zoster (chicken pox),yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonalinfluenza vaccines for injection are generally killed virus vaccines and areallowed; however, intranasal influenza vaccines (eg, FluMist®) are liveattenuated vaccines and are not allowed. Experimental and/or nonauthorizedcoronavirus disease (SARS-CoV-2) vaccinations are not allowed.

• Receiving immunosuppressive drugs or systemic corticosteroids such asprednisone at doses > 25 milligrams (mg) daily or its equivalent within 14 daysprior to the first dose of GEN1160.

• History of symptomatic autoimmune disease (eg, rheumatoid arthritis, systemicprogressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren'ssyndrome, autoimmune vasculitis [eg, Wegener's granulomatosis]).

• Has clinically significant cardiac disease, including:

• Myocardial infarction within 6 months prior to the first dose of GEN1160, orunstable or uncontrolled disease/condition related to or affecting cardiacfunction (eg, unstable angina, congestive heart failure, New York HeartAssociation Class III or IV), cardiac arrhythmia (Common Terminology Criteriafor Adverse Events [CTCAE] Version 5.0 Grade 2 or higher), or clinicallysignificant electrocardiogram (ECG) abnormalities.

• Screening 12-lead ECG showing a baseline QT interval as corrected by QTcF > 480milliseconds (msec).

• Echocardiogram (ECHO) or multigated acquisition (MUGA) scan with leftventricular ejection fraction (LVEF) < 45%.

• Has clinically significant toxicities from previous anticancer therapies that havenot resolved to baseline levels or to Grade 1 or lower. Note, participants with ≤Grade 2 neuropathy or alopecia are an exception to this criterion and may qualifyfor the trial.

• Active graft versus host disease (GVHD) requiring immune suppression regardless ofgrade.

Note: Other protocol-defined Inclusion and Exclusion criteria may apply.