*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: Sparrow, St. John, Macomb, GenHur, Hurley, LVHN, SJMH (Ann Arbor, Brighton, Canton, Chelsea), Livonia, SJMO

Eligibility Criteria:

Disease Related Criteria

a. Participants must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) which is Stage IV or recurrent.

Prior/Concurrent Therapy Criteria

a. Participants must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for any stage of NSCLC. Anti-PD-1 or anti-PD-L1 may have been given alone or in combination with other therapy.

b. Participants must not have received more than one line of anti-PD-1 or anti-PD-L1 for Stage IV or recurrent disease.

c. Participants must have experienced disease progression (in the opinion of the treating physician) more than (>) 84 days following initiation (Cycle 1 Day 1) of their most recent anti-PD-1 or PD-L1 therapy.

d. Participants who received anti-PD-1 or anti-PD-L1 therapy for Stage IV or recurrent disease, must have had a best response on anti-PD-1 or anti-PD-L1 therapy of stable, partial response or complete response (in the opinion of the treating physician).

e. Participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy as their only line of anti-PD-1 or anti-PD-L1 therapy must have experienced disease progression within (<=) 365 days from initiation (Cycle 1 Day 1) of anti-PD-1 or PD-L1 therapy.

f. Participants must have received platinum-based chemotherapy and experienced disease progression (in the opinion of the treating physician) during or after this regimen. g. Participants with a known sensitizing mutation for which an FDA-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 and MET sensitizing mutations), must have previously received at least one of the approved therapy(s). Prior targeted therapy for participants with targetable alterations is allowed if all other eligibility criteria are also met.

h. Participants must not be receiving or planning to receive another investigational therapy during study participation.

Clinical/Laboratory Criteria

a. Participants must be ≥ 18 years old.

b. Participants must be able to safely receive the investigational drug combination and the investigator’s choice of standard of care regimens described in Section 7.2, per the current FDA-approved package insert(s), treating investigator’s discretion, and institutional guidelines.

c. Participants must have Zubrod Performance Status of 0-2 (see Section 10.3).  

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: Trinity Health IHA (Ann Arbor, Brighton, Chelsea, Canton) and Livonia, Genesys, Hurley, sparrow

Eligibility Criteria:

5.1. Disease Related Criteria

a. Participants must have advanced or locally unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma.

b. Participants must have PD-L1 CPS (Combined Positive Score) ≥ 1. This test would have been performed as part of SOC pathology testing, using tissue obtained within two years prior to registration and collected prior to or after a frontline regimen.

c. Participants must have a histologically confirmed diagnosis of MSS and HER2 negative gastric, gastroesophageal junction, or esophageal adenocarcinoma.

d. Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 28 days prior to registration for participants with measurable disease. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form.

e. Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after CNS-directed therapy. All treatment for brain metastases must have been completed at least 28 days prior to registration.

5.2. Prior/Concurrent Therapy Criteria

a. Participants must have disease progression or intolerance to frontline standard of care (SOC) chemotherapy plus either nivolumab, pembrolizumab or any other PD-1 or PD\u0002L1 inhibitor. Peri-operative chemotherapy plus nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor will count as one line if disease progression occurs while on the therapy or within 6 months of completing the chemotherapy plus nivolumab or pembrolizumab or other PD-1/PD-L1 inhibitor cycle.

b. Participants must not have received more than one prior line of systemic therapy.

c. Participants must not have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if <10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of ≥7 days prior to registration.

d. Participants must not have prior significant immunotherapy related adverse events requiring permanent discontinuation of the immunotherapy agent including events like pneumonitis, myocarditis, renal failure, Guillain barre syndrome, or myasthenia gravis. Participants with endocrinopathy events leading or not to replacement steroids, thyroid hormone, insulin, or cortisol are eligible.

e. Participants must not have received a live attenuated vaccination within 28 days prior to registration (See Appendix 18.5).

f. Participants must not have had a major surgery within 28 days or subcutaneous venous access device placement within 7 days prior registration.

g. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator. Any participants with postoperative bleeding complications or wound complications from a surgical procedure performed in the last eight weeks should be excluded.

h. Participants must not have plans to undergo elective or planned major surgery during the clinical trial.

i. Participants must not have active bleeding or prior history of GI perforation, fistula or significant GI bleeding (requiring transfusion, endoscopic or surgical intervention) within 84 days prior to registration.

j. Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, investigational agents, biologic or hormonal therapy for cancer treatment while receiving treatment on this study.

k. Participants must not have a history of a Grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy.

l. Participants must not have a history of grade 3 or 4 immunotherapy related toxicities with the exception of hormonal abnormalities like thyroiditis or thyroid derangements.

5.3. Clinical/Laboratory Criteria

a. Participants must be ≥ 18 years old.

b. Participants must have Zubrod Performance Status of 0-2 (see Section 10.5).

c. Participants must have a complete medical history and physical exam within 28 days prior to registration.

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST**

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health SJMH IHA (Brighton, Ann Arbor, Chelsea, Canton), Livonia, Genesys, Sparrow

Eligibility Criteria:

5.1. Disease Related Criteria

a. Participants must have a histologically confirmed diagnosis of Classic Follicular Lymphoma (cFL). cFL was previously categorized as Grade 1-3A per WHO-HAEM4R, but grading of classic FL is no longer mandatory. Please refer to Section 4.1 regarding classification. NOTE: Participants with Follicular Lymphoma with uncommon features (uFL) are eligible, including FL with diffuse growth pattern (dFL). Diagnosis is as per local pathology. Lymphoma FISH is not required. Molecular testing is not required.

b. Participants must not have Follicular Lymphoma with “blastoid” or “large centrocyte” cytological features, or Follicular large B-cell lymphoma (FLBL) (Previously categorized as follicular lymphoma grade 3B).

c. Participants must have low-tumor burden follicular lymphoma defined as:

1. Nodal or extra-nodal tumor mass with diameter less than 7 cm in its greater diameter

2. Involvement of no more than 3 nodal or extra nodal sites with diameter greater than 3 cm.

3. Absence of B symptoms

4. No symptomatic splenomegaly

5. No compression syndrome (ureteral, orbital, gastrointestinal)

6. No pleural or peritoneal serous effusion related to follicular lymphoma Participants must have Ann Arbor stage II, III, or IV follicular lymphoma. Participants with Stage I disease may be included if they do not wish to undergo radiation or are not candidates for radiation. Please refer to Section 4.2 regarding staging classification.

d. Participants must either be experiencing distress due to their disease or would prefer active management of their disease rather than a watch and wait approach.

e. Participants must have staging imaging performed within 49 days prior to registration, as follows. PET-CT baseline scans are preferred. If a baseline PET-CT scan cannot be obtained, CT scans of the chest, abdomen, and pelvis, along with a bone marrow biopsy, are acceptable. If CT scans are used for staging at baseline, a CT scan of the neck is recommended. All measurable dominant lesions must be assessed within 49 days prior to registration (see Section 10.1a.). Tests to assess non-measurable disease must be performed within 49 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. NOTE: if the initial evaluation is insufficient to detect measurable disease, treating investigators may obtain a CT scan with contrast.

f. Participants must have bi-dimensionally measurable disease (at least one lesion with longest diameter >1.5 cm).

5.2. Prior/Concurrent Therapy Criteria

a. Participants must not have had prior systemic therapy for follicular lymphoma. Radiation therapy for a previous diagnosis of early-stage follicular lymphoma is allowed.

5.3. Clinical/Laboratory Criteria

a. Participant must be ≥ 18 years of age at the time of registration.

b. Participant must have Zubrod Performance Status of 0-2 (see Section 10.4).

c. Participant must have a complete medical history and physical exam within 28 days prior to registration.

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST**

Eligibility Criteria:

a. Disease Related Criteria

1. Participants must have a histologically confirmed diagnosis of prostate cancer at the time of Step 1 Registration.

2. Participants must have castrate-resistant prostate cancer and metastatic disease by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node).

b. Prior/Concurrent Therapy Criteria

1. Participants may have received any prior therapy, but one must be docetaxel or contain docetaxel in either the castrate-sensitive and/or castrate resistant disease state.

c. Clinical/Laboratory Criteria

1. Participants must be ≥ 18 years of age at the time of Step 1 Screening Registration.

d. Specimen Submission Criteria  

1. Participants must have solid tumor biopsy material (formalin-fixed paraffin\u0002embedded (FFPE) tissue blocks and/or 10 cut slides on four-micron thick unstained positive charged slides of FFPE tissue) available for submission for alterations in TP53, RB1 and PTEN by IHC using CLIA certified assays in the MD Anderson Clinical Pathology Laboratory. This specimen is required for central assessment of the AVPC-MSIHC regardless of whether the site has already locally evaluated the AVPC-MS status.

2. Tumor samples submitted for analysis must have been collected within 12 months prior to Step 1 Screening Registration. Samples from metastatic lesions collected in the castrate-resistant disease state are preferable but not mandatory. Samples obtained during the hormone-naïve disease state are acceptable if collected within 12 months of Step 1 Screening Registration. If more than one tumor sample exists, the sample obtained closest to the date of registration should be submitted to MDACC for analysis.

NOTE: Sites will receive an email from SWOG Statistics and Data Management Center containing participant results of Aggressive Variant Prostate Cancer Molecular Signature (AVPC-MS) assessment within 5-12 business days after tissue submission to MD Anderson Clinical Pathology Laboratory. The participant's AVPC-MS signature result (Positive or Negative) is required BEFORE randomization on to Step 2. If sites receive a non-evaluable AVPC-MS signature result, SWOG Statistics and Data Management Center will provide instructions for resubmission.  

a. Disease Related Criteria

1. Participants must have castrate levels of testosterone with a baseline level 50ng/dL within 28 days prior to Step 2 Randomization.

2. Participants must have evidence for metastatic prostate cancer by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). Visceral and/or soft-tissue metastases must be ≥1.0 cm in diameter and lymph nodes must be >1.5 cm diameter in the short axis. Scans must be obtained within 28 days prior to randomization. 

NOTE: All disease must be assessed and documented on the Baseline/Pre-Registration Tumor Assessment Form.

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health SJMH IHA (Brighton, Ann Arbor, Chelsea, Canton), Livonia, Genesys, Sparrow

Eligibility Criteria: 

5.1. Disease Related Criteria

a. Participants must have histologically or cytological confirmed diagnosis of clinical Stage II-IIIB (excluding clinical N3 disease) (as defined in Section 4.0) non-small cell lung cancer (NSCLC).

b. Participants must have had a complete (R0) resection of NSCLC (with appropriate lymph node sampling as defined by the NCCN Guidelines) within 84 days (12 weeks) prior to randomization. Acceptable types of surgical resection are: lobectomy, sleeve resection, bi-lobectomy, or pneumonectomy. Wedge resection is not allowed. Note the NCCN Guidelines: N1 and N2 node resection and mapping is a routine component of lung cancer resections. It is recommended at a minimum one N1 and three N2 stations is sampled or complete lymph node dissection. Formal ipsilateral mediastinal lymph node dissection is indicated for participants undergoing resection for N2 disease.

c. Participants must have a pathologic complete response (pCR) (no viable tumor in the resected specimen or lymph nodes), as determined by local pathology review.

d. Participants must have a PD-L1 status result (e.g. (1% versus >= 1% or unknown).

e. Participants must not have known EGFR mutations, or ALK gene fusion.  

5.2. Prior/Concurrent Therapy Criteria

a. Participants must have received at least two cycles of neoadjuvant platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy. The neoadjuvant treatment must be FDA approved and standard of care as listed in NCCN guidelines.

b. Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for NSCLC treatment while receiving treatment on this study.

c. Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 28 days prior to randomization.

d. Participants must not have medical contraindications or severe adverse events to receiving anti-PD-1 or anti-PD-L1 therapy. 

e. Participants must not have received post-operative radiation therapy (PORT) for NSCLC.

f. Participants must not have any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, and vitiligo. Note, participants with Grade ≥2 neuropathy may be included at the discretion of the treating investigator. Note, participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the discretion of the treating investigator.

5.3. Clinical/Laboratory Criteria

a. Participant must be ≥ 18 years old at time of study entry.

b. Participants must have body weight > 30 kg.

c. Participants must have Zubrod Performance Status of 0-2 (see Section 10.2).

d. Participants must have a complete medical history and physical exam within 28 days prior to randomization.  

**PLEASE SEE CURRENT VERSION OF PROTOCOL FOR FULL ELGIBILITY LIST** 

1.0) Histo or cyto dx of Stage IIIa or IIIb NSCLC CA involving superior sulcus (T3-4, N0-1)
2.0) Mediastinal/Supraclavicular nodal invol (N2/N3 Dx) NOT ELIGIBLE
3.0) Parenchymal lesions = 2 same or both lungs NOT ELIGIBLE
4.0) Must have mediastinal exploration 42 days prior to registration.
5.0) No evidence of distant mets found 42 days prior to registration.
6.0) Must have measurable dz.

7.0) No prior chemo or RT allowed.
8.0) PS 0-2.

Drugs: CDDP, VP-16

9.0)
10.0)
11.0)

1.0) Pt must be randomized to this study = 5 days from randomization to S9623.
2.0) Prestudy bone marrow speciman must be submitted.

**Long term follow up study only. See SWOG website for list of Applicable Treatment Trials **

(S0221, S0307, S0800, S0812, S1310, S9921, S0925, S0033)

-Newly diagnosed primary breast cancer prior to initial definitive surgical treatment, including In situ and Invasive cancer, Stages 0 - III. Pathologic confirmation of diagnosis is required.
-Patients must be able to read and write in English or Spanish
-Patients must not have received HBOC genetic counseling or mutation testing prior to diagnosis. If the patient was previously tested only for a variant of uncertain clinical significance (i.e., not for known familial mutation, Jewish ethnicity panel/Multisite 3 or comprehensive sequencing) and documentation is provided, they remain eligible.

Due to IP storage conditions, patients should be treated in Ann Arbor only.

Adverse events of special interest (AESI) in this study include the following events:

• Hyperglycemia Grade ≥3

• Hypoglycemia Grade ≥2 All glucose AESIs, as defined above, will be reported using the same procedures as for SAEs (see Section 9.2), even if seriousness criteria are not met.

• Thrombocytopenia Grade ≥2

• Rash Grade ≥2 or considered related to one or more study drugs

• Diarrhea Grade ≥2 or considered related to one or more study drugs

• Mucositis Grade ≥2 or considered related to one or more study drugs

 These events will be documented on the AESI page of the eCRF.