Fitness-adapted, Pembrolizumab-based Therapy for Untreated Classical Hodgkin Lymphoma Patients 60 Years of Age and Above

Inclusion Criteria:

• Participants of any sex who are ≥60 years of age on day 1, cycle 1.

• The participant must be willing and able to provide written informed consent for thetrial and participate in all planned study procedures.

• Histologically confirmed diagnosis of classical Hodgkin lymphoma

• PET-avid, measurable disease (≥1.5cm bi-dimensional measurement)

• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to

• PS 2 may be allowed at the discretion of the treating investigator if impairment isconsidered to be primarily lymphoma-related. Evaluation of ECOG is to be performedwithin 10 days prior to the date of registration.

• Participants who have received involved field radiation will be allowed. However,they will be excluded if any of the following are true:

1. Radiation was dosed ≤6 months from registration.

2. Radiation was delivered to > 1 lymph node group as defined by the NCCNcriteria.

3. The radiation dose was ≥30 Gy.

4. The participant has radiation-related toxicities ≥ Grade 2 at the time ofregistration.

5. The participant requires corticosteroids for radiation-related toxicities atthe time of registration (regardless of dose).

6. The participant has ever experienced radiation pneumonitis.

• Have adequate organ function as defined per protocol. Specimens must be collectedwithin 10 days prior to registration (confirmation of eligibility).

Exclusion Criteria:

• Nodular lymphocyte-predominant Hodgkin lymphoma

• Life expectancy < 6 months for any reason excluding lymphoma

• Has received prior therapy with an immune checkpoint inhibitor, against targetsincluding but not limited to PD1, PDL1, PDL2, CTLA-4, OX40, or LAG 3 unless givenwith curative intent for reasons other than lymphoma AND the last dose was more than 3 years from registration. Any participant who received prior immune checkpointinhibitor therapy will be excluded if they experienced any toxicity related to orpossibly related to the immunotherapy that required discontinuation of drug.

• Prior systemic therapy for cHL, with the exception of steroids

• If participant received major surgery, they must have recovered adequately from thetoxicity and/or complications from the intervention prior to starting studytreatment.

• Presence of Grade ≥ 2 sensory and/or motor neuropathy

• Prior solid organ or stem cell transplant.

• Clinical suspicion or evidence of active involvement of lymphoma into the spinalcord, cerebral spinal fluid, or brain. External compression of the spinal cord ornerve roots is not considered involvement.

Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines, subunit vaccines, and nucleic acid vaccines is allowed.

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study treatment.

Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent [excluding steroids neededfor lymphoma related symptoms]) or any other form of immunosuppressive therapywithin 7 days prior to the first dose of study drug.

• Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years. Note: Participants with basal cell carcinoma of the skin,squamous cell carcinoma of the skin or carcinoma in situ (excluding carcinoma insitu of the bladder) that have undergone potentially curative therapy are notexcluded.

• Has known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of itsexcipients.

• Has active autoimmune disease that has required systemic treatment in the past 2years (i.e. with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment.

• Interstitial lung disease or a history of (non-infectious) pneumonitis/interstitiallung disease that required steroids or has current pneumonitis/interstitial lungdisease.

• Any known history of pancreatitis as defined by Gandhi et al. 201432,36.

• Has an active infection requiring oral or intravenous systemic therapy.

• Has a known history of Human Immunodeficiency Virus (HIV).

• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] isdetected) infection. Prior exposure to hepatitis B is allowed as long as there areno HBsAg detected (ie positive Hepatitis B core antibody with negative HBsAg). Priortreatment with Hepatitis C is allowed if the screening HCV RNA by PCR is negative.

• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis).

• Is currently taking a strong CYP3A4 modulator. Subjects taking strong CYP34Amodulators that can safely stop these medications prior to treatment should completea washout period of 4 weeks or 5 times the half-life of a particular drug, whicheveris shorter.

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with theparticipant's participation for the full duration of the study, or is not in thebest interest of the participant to participate, in the opinion of the treatinginvestigator.

• Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of trial treatment.

Note: given older age at enrollment, WOCBP are not anticipated to enroll on this study.