Study of Intratumoral G100 With Or Without Pembrolizumab or Rituximab In Participants With Follicular Non-Hodgkin's Lymphoma (MK-3475-174/IMDZ-G142)

Inclusion Criteria:

1. Follicular low-grade NHL:

   • In Part 1-3: either treatment naïve (except for France) OR relapsed or refractory following at least one prior treatment.
   • In Part 4, enrollment is limited to relapsed OR refractory follicular NHL participants.
   • In Part 5, enrollment will include relapsed and refractory CD20+ follicular NHL following at least one but not more than 2 prior treatments.

2. Tumor mass(es) accessible for intratumoral injection

   • For Part 1-3, are being considered for local radiation therapy and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response.
   • For Part 4 and 5, radiation therapy is omitted. Measurable tumor mass(es) accessible for intratumoral injection must be present for treatment and assessment of response.
3. ≥ 18 years of age
4. Life expectancy of ≥ 6 months per the investigator
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Electrocardiogram (ECG) without evidence of clinically significant arrhythmia or ischemia
7. If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use two methods of birth control or is considered highly unlikely to conceive during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment
8. If male and sexually active with a FCBP, must agree to use highly effective contraception such as latex condom or is sterile (e.g. following a surgical procedure) during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment

Exclusion Criteria:

1. Cancer therapies, including chemotherapy, radiation (non-study regimen related), biologics or kinase inhibitors, granulocyte-colony stimulating factor (G-CSF) or granulocyte/monocyte-colony stimulating factor (GM-CSF) within 4 weeks prior to the first scheduled G100 dose
2. Investigational therapy within 4 weeks prior to G100 dosing
3. Prior administration of other intratumoral immunotherapeutics

4. Inadequate organ function including:

   1. Marrow: Peripheral blood leukocyte count (WBC) < 3000/mm^3, absolute neutrophil count ≤ 1500/mm^3, platelets < 75000/mm^3, or hemoglobin < 10 gm/dL
   2. Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x Upper Limit of Normal (ULN), total serum bilirubin > 1.5 x ULN (participants with Gilbert's Disease may be included if their total bilirubin is ≤3.0 mg/dL)
   3. Renal: Creatinine > 1.5x ULN
   4. Other: INR (international normalized ratio) or partial thromboplastin time (PTT) >1.5 x ULN

5. Significant immunosuppression from:

   1. Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or
   2. Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine or conditions such as common variable hypogammaglobulinemia
6. Pregnant or nursing
7. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
8. History of other cancer within 2 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ)
9. Recent (<1 week ago) clinically significant infection, active tuberculosis or evidence of active hepatitis B, hepatitis C or HIV infection
10. Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease.
11. Significant autoimmune disease, including active non-infectious pneumonitis, with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy
12. Psychiatric, other medical illness or other condition that in the opinion of the principal investigator (PI) prevents compliance with study procedures or ability to provide valid informed consent
13. History of significant adverse or allergic reaction to any component of G100 and, if enrolled in Part 2 or Part 4, pembrolizumab and/or any of its excipients, and if enrolled in Part 5, anti-CD20 antibodies including rituximab and/or any of its excipients

14. Use of anti-coagulant agents or history a significant bleeding diathesis. (If a superficial lymph node or subcutaneous mass is to be injected, participants on agents such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or clopidogrel are eligible and these agents do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Medical Monitor and may need to be discontinued before G100 therapy.

    For participants enrolled in Part 2 or Part 4 with the potential to receive pembrolizumab:

15. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis or interstitial lung disease
16. Received a live virus vaccine within 30 days of planned study start
17. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft vs. host disease [GVHD]).
18. Has had an allogeneic tissue/solid organ transplant
19. Has received prior therapy with an anti-PD-1, anti-programmed death ligand (PD-L)1, or anti-PD-L2 agent or if the participant has previously participated in Merck MK-3475 clinical trials or was previously treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event.